Radiology Resident Case of the Week
Etiology/Pathophysiology:
Hepatobiliary scintigraphy for biliary atresia and/or neonatal hepatitis utilizes the biochemical properties of the iminodiacetic acid (IDA) derivatives developed originally as cardiac imaging agents. The IDA portion of these agents, an analogue of lidocaine, is the "non-active" carrier portion of the molecule providing the proper "philicity" for the molecules to reach the liver. It is the ligand which is chelated to the IDA which makes these agents analogues of bilirubin allowing heptocyte uptake by the same active transport mechanism as non-conjugated bilirubin itself.
The most recent radiopharmaceutical, mebrofenin, labelled with Tc-99m, provides the greatest percentage of liver accumulation (> 98%) up to very high levels of hepatic dysfunction as evidenced by serum total bilirubin levels of 25mg/dl.
In biliary atresia versus severe neonatal hepatitis, there may be a discrepancy in localization of the radiotracer in the liver owing to the somewhat different mechanism for hyperbilirubinemia. Biliary atresia does not have true hepatocellular dysfunction such that tracer accumulation in the liver should be normal whereas in neonatal hepatitis there is abnormal liver function leading to depressed hepatocellular accumulation of tracer and delayed transit through the liver.
Pathology:
Biliary atresia is characterized by absent bile ducts most notable within the liver hilum. Despite this atretic obstruction, the intrahepatic biliary ducts are present but small rather than dilated. The gallbladder is severely hypoplastic or absent.
In neonatal hepatitis, there is inflammatory cell infiltration of the hepatocytes with associated necrosis and bile stasis although the bile ducts are normal and patent.
Recent investigations have defined an entity called "biliary hypoplasia" having a histologic presentation between neonatal hepatitis and biliary atresia. The ducts are small and the hepatocytes have significant inflammatory changes although considerably less than in neonatal hepatitis alone. In fact, in many cases of biliary atresia, some multinucleated giant cells may be present with a component of hepatocellular necrosis. This has led some investigators to believe that biliary atresia and neonatal hepatitis may be opposite extremes of the same pathophysiologic process and that "biliary hypoplasia" represents an overlap of these two processes. In fact, these two entities cannot be separated by clinical or laboratory criteria.
Miscellaneous:
Some investigators advocate the administration of phenobarbital to neonates with hyperbilirubinemia prior to biliary scintigraphy to improve hepatocellular extraction of the radiotracer. The recommended dose is 5 mg/kg per day for 5 days prior to the study.
It is important to separate biliary atresia from other causes of newborn hyperbilirubinemia as there is progressive cirrhotic changes of the liver in infants who do not receive treatment before 3 months of age.
Imaging:
Unlike laboratory or clinical criteria, hepatobiliary scintigraphy is very sensitive (80-95%) in separating biliary atresia from neonatal hepatitis.
1) The hepatocellular accumulation of radiotracer may be better in biliary atresia than neonatal hepatitis as the former is not characterized by cellular dysfunction whereas the latter is. This imaging criterion is suspect at best.
2) More importantly, the imaging criterion which separates these two disease entitities and which provides a high imaging sensitivity is the appearance of biliary ductal and bowel activity. Although the radiotracer accumulation within the liver is excellent in biliary atresia, bowel activity should not be seen because of the atretic ducts. On the other hand, the hepatocellular dysfunction in neonatal hepatitis causes slow biliary excretion of tracer and stasis in the bile ducts, however, bowel activity will eventually be seen because the ducts are patent.
As shown in the example case there is excellent radiotracer (Tc-99m Mebrofenin) accumulation in the liver but no bowel activity at 15 hours. The activity seen within the lower mid abdomen is bladder and urine contaminated diaper (5.5 and 15 hours) as there is a small amount of tracer excretion by the kidneys. This should not be confused with bowel activity.
Most investigators advocate imaging to 24 hours to provide the greatest imaging sensitivity for biliary atresia versus neonatal hepatitis. Imaging beyond this point is not recommended as the 6 hour half-life of Tc-99m limits the available tracer for good imaging.
DDx:
Common:
Uncommon:
Rare:
All of the above will cause hyperbilirubinemia in the newborn, however, hepatobiliary scintigraphy with delayed imaging to demonstrate bowel accumulation of tracer should separate biliary atresia from the other entities with a high degree of sensitivity. Unfortunately, there may still be false postives, as for example in very severe obstruction sometimes seen in bile plug syndrome or cystic fibrosis, or very severe hepatocellular dysfunction.
Key references:
Miller JH, Gelfand MJ. Pediatric Nuclear Imaging. Philadelphia: W.B. Saunders, 1994: Chapter 6.
ACR Code:
Biliary atresia 7.1434
Keywords:
biliary atresia, neonatal hepatitis, hepatobiliary scintigraphy