Development of a reliable means for functional assessment of liver performance after Fontan operation: dual cholate clearance assay

With vastly improved survival for babies born with congenital heart disease (CHD), there is increasing attention on long-term outcomes in adulthood, especially those born with severe forms of CHD. One area of intense research is liver disease in Fontan patients, the nature of which is incompletely understood. It is known that these patients are at risk for advanced fibrosis (scarring) and even cirrhosis and these risks increase over time as patients grow older. However, there is a paucity of data exploring the relationship between liver appearance (scar and extent of scar as assessed by ultrasound, MRI or CAT scans, liver biopsy) and liver function and performance (how well the liver clears toxins from the blood as assessed by standard blood tests). There is research to suggest that liver appearance by imaging and biopsy may not accurately predict liver function in the Fontan and that these two aspects of the liver are uncoupled (i.e. patients with much liver scarring may have reasonably good function, and vice versa). Furthermore, by the time laboratory abnormalities are found in the blood, liver disease may be advanced and it could be too late. A novel test called HepQuant® is an assay used to measure liver function in other types of liver disease and has been shown to predict liver-related complications in these patients. In these populations, the assay may be able to predict more subtle or sub-clinical liver abnormalities that blood tests cannot detect. HepQuant® is a test that examines the ability of the liver to process a substance called cholate, which is a naturally occurring substance in the body. Cholate gets to the liver 2 ways: through the gut (by mouth) or through the blood (IV or intravenous). The test involves administering oral and IV cholate which is labeled. This label is NOT radioactive, but can act as an indicator/marker for evaluation purposes. Blood is then drawn at multiple time points after administration of the cholate. If the liver has good function, then clearance of cholate will be high. Similarly if the liver is not functioning well, clearance of cholate will be low. The amount of clearance is then converted to a disease score.