Benjamin Aubey, MD

The mother of a 1-month-old girl brought the baby to the clinic mistakenly thinking that she was scheduled for her first well-child visit. There was no appointment scheduled but her pediatrician agreed to see the child. The baby seemed to be healthy; she was feeding well on formula milk and was developmentally normal for her age.

The infant appeared alert and active. Her weight, length, and head circumference plotted at 50th percentile. She had mildly yellowish sclera but there was no other clinical evidence of jaundice. There was no hepatosplenomegaly noted and the remainder of the examination was normal. After the examination, the infant passed very pale stool while the mother was changing her diapers 

The mother said that the baby’s stools had been a yellowish color until about 2 weeks after birth when they started to turn pale. The mother had not noticed any change in the baby's skin and eye color since birth and couldn’t recall any other symptoms that had alarmed her. The baby’s urine was noted to be light yellow.

Liver enzymes and serum bilirubin levels were measured immediately. Results found AST, 221 IU/L (normal range, 15 to 60 IU/L); ALT, 124 IU/L (normal range, 13 to 45 IU/L); and ALP, 502 IU/L (normal range, 150 to 420 IU/L). The total bilirubin level was 8.2 mg/dL and direct bilirubin was 5.1 mg/dL.

The differential diagnosis at this stage was: biliary atresia, neonatal hepatitis, alagille syndrome, choledochal cyst, sclerosing cholangitis, tyrosinemia, cystic fibrosis.

1. What other lab tests would you order? 
2. Would you consider imaging for this patient? If so, which one(s)?
3. What's your diagnosis? 
 

The infant was admitted to the hospital. Abdominal ultrasonography showed liver fibrosis and a small, indistinct gallbladder. Findings of a hepatobiliary iminodiacetic acid (HIDA) scan showed an absence of transit of the dye from the biliary system to the bowels. Taken together, the findings of these 2 studies created a high suspicion for biliary atresia. The infant was given IV phenobarbital and oral ursodiol.

During the following 5 days the infant’s stools remained intermittently chalky in color. The urine remained yellow and clear. A urinalysis showed 1+ bilirubin. Serial bilirubin measures showed a slow decline in both direct and total bilirubin levels in response to the phenobarbital and ursodiol. The child appeared clinically well during the hospital stay and had normal feeding, stooling, and voiding patterns. Results of a repeat HIDA scan 5 days after hospital admission were unchanged and a decision was made to transfer the child to another medical institution for a hepatic portoenterostomy (HPE) of the Kasai procedure. The day before the transfer, her total bilirubin level was 5.6 mg/dL and direct bilirubin was 3.5 mg/dL.

The child tolerated the procedure well. She was discharged on a hypoallergenic lactose-free formula, ursodeoxycholic acid, and multivitamin supplements.

When bile levels are low or completely absent from the GI tract, stools become acholic, or pale or clay-colored.

There are 2 main pathophysiologic mechanisms behind poor bile transit: 
1.  Absence of bile secondary to a production defect
2. Anatomical blockage in the biliary system.

In biliary atresia, the flow of bile from liver to small intestine is obstructed. There are 2 types of biliary atresia:

. This form is associated with laterality abnormalities and is thus thought to be genetic.

. This form (also known as neonatal or perinatal biliary atresia) is more common-it occurs in 80% of cases. The biliary system is normal at birth and is thought to be damaged later by a viral infection that triggers inflammation, scarring, and fibrosis. Most affected babies have birth weights that are appropriate for their gestational ages and are delivered at term. Surprisingly most jaundiced infants with biliary atresia appear well. The first and most common sign of biliary atresia is jaundice. Acholic stools, another classic finding, are more difficult to see since they may present intermittently, alternating with stools of a normal color. Darkened urine is also easily missed since most parents dismiss the yellow staining of the diapers. 

The initial evaluation of a patient with suspected biliary atresia should include immediate evaluation of serum bilirubin levels and liver enzymes. Values for PT/PTT and serum albumin level should also be checked to assess the liver function. Neonatal hepatitis should be ruled out by measuring antibody titers for TORCH infections and with HSV smears and urine CMV cultures.


The 2 most useful imaging studies are ultrasonography of the liver and the extrahepatic biliary tree and a HIDA scan. The HIDA scan involves the injection of a dye that circulates to the liver where it is eventually secreted into the biliary tree allowing visualization of the gallbladder and the entire biliary system. Delayed uptake occurs when there is hepatocellular damage as seen in neonatal hepatitis and in the latter stages of obstructive cholestasis. Failure to secrete the dye from the liver to the small intestine indicates an obstruction and is suggestive of biliary atresia. If results of these studies are equivocal, a liver biopsy may be required to provide a definitive diagnosis.

 
Hepatic portoenterostomy (HPE) as described by Kasai can help restore bile flow and delay the progression of liver disease in children with biliary atresia. Prognosis is significantly better if surgery is performed within the first 60 days of life. If successful, bile drainage is achieved and cholestasis improves. If jaundice persists 3 months after Kasai HPE, liver transplant should be considered since a direct bilirubin level greater than 2.0 mg/dL is predictive of a drastically reduced 2-year survival rate (20% vs 80%). However, even if a Kasai HPE is initially successful, at least half of these patients will have slowly progressive liver disease and will ultimately require liver transplantation within 2 years of the procedure. The most common indications for a liver transplant are: primary failure of a Kasai HPE, growth failure, portal hypertension, and progressive liver disease. 
 
Early diagnosis is paramount since outcomes of a Kasai HPE are better if it is performed before the child is 60 to 90 days of age. Prognosis for a child diagnosed after 100 days is ominous. Kasai procedures performed after 90 to 120 days have worse outcomes with direct bilirubin measurements 3 months post-surgery predictive of long-term survival.

 Zallen GS, Bliss DW, Curran TJ, et al. Biliary atresia. PediatrRev. 2006;27:243-248.

Wadhwani SI, Turmelle YP, Nagy R, et al.  Prolonged neonatal jaundice and the diagnosis of biliary atresia: a single-center analysis of trends in age at diagnosis and outcomes. Pediatrics. 2008;121:e1438-e1440.

Haber BA, Erlichman J. Biliary Atresia. Up-To-Date. Available at http://www.uptodate.com/contents/biliary-atresia.  Accessed June 10, 2011.

Benjamin Aubey, MD

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A 1-Month Old Girl With Acholic Stools