Bile acids are water-soluble components of bile that are derived from cholesterol metabolism by liver cells. Two primary bile acids are formed: cholic acid and chenodeoxycholic acid. Both are conjugated with glycine or taurine molecules and excreted from liver cells into bile in a manner similar but not identical to bilirubin excretion. The conjugated bile acids are stored in the gallbladder with bile and released into the duodenum, where they help to absorb fat and fat-soluble material. About 95% of the bile acids are reabsorbed from the jejunum and ileum and taken through the portal vein back to the liver, where they are reextracted by liver cells and put back into the bile. Cholic acid is reabsorbed only in the terminal ileum. A small proportion of circulating bile acids is excreted by the kidneys and a small proportion reaches the colon, where is undergoes some additional changes before being reabsorbed and taken back to the liver.

At least two cycles of bile acid metabolism occur in the 2 hours following a meal. Normally, 2-hour postprandial bile acid levels are increased 2-3 times fasting levels. Even so, the values are relatively low.

Due to the metabolic pathways of bile acids, diseases affecting hepatic blood flow, liver cell function (bile acid synthesis), bile duct patency, gallbladder function, and intestinal reabsorption can all affect serum bile acid levels. However, intestinal malabsorption is uncommon and usually does not simulate liver disease. Although gallbladder disease (cholecystitis or cholelithiasis) can occasionally mimic liver disease and may be associated with common bile duct obstruction, most cases of primary gallbladder disease can be differentiated from primary liver disease. Therefore, bile acid abnormality is relatively specific for liver or biliary tract disease. Both cholic acid and chenodeoxycholic acid can be measured by immunoassay techniques. Cholic acid assay is more readily available at the present time. The assays are not widely available but can be obtained in university centers or large reference laboratories. Because values fluctuate during the day and are affected by food, specimens should be obtained at the same time of day (usually in the early morning) and the same relationship to meals.

Bile acid assay is said to be the most sensitive test available to detect liver or biliary tract dysfunction. The 2-hour postprandial level is more sensitive than the fasting level, which itself is more sensitive than any one of the standard liver function tests. In most reports serum bile acid, even using a fasting specimen, was 10%-20% more sensitive than any other single liver function test in various types of liver and biliary tract conditions. There are only a few investigators who report otherwise. Bile acids are frequently abnormal in inactive cirrhosis when all other biochemical liver tests are normal and are frequently abnormal in resolving hepatitis when other tests have subsided below the upper limits of their reference ranges. Bile acid assay has mostly replaced bromsulphalein (BSP) and indocyanine green (CardioGreen) for this purpose. A normal bile acid assay, especially the 2-hour postprandial value, is excellent evidence against the presence of significant liver or biliary tract disease. There have not been sufficient studies to establish the exact sensitivity of bile acid assay in early metastatic tumor to the liver. The major advantages of bile acid assay, therefore, are its sensitivity in most types of liver and biliary tract disease and its relative specificity for the liver and biliary tract. One report indicates that bile acids may be elevated by phenytoin or isoniazid therapy.

Bile acid assay might also be useful to prove liver origin of abnormal liver function test results in those cases where tests like GGT are equivocal or are affected by nonhepatic conditions that could produce falsely elevated values. Bile acid assay could theoretically be used to differentiate jaundice due to hemolysis from that due to liver disease but is rarely necessary for this purpose. Bile acid assay has been suggested as a test for intestinal malabsorption, but few reports are available on this subject.

The major drawback of bile acid assay is lack of ability to differentiate among the various types of liver or biliary tract disease. Bile acid assay cannot differentiate between intrahepatic and extrahepatic biliary tract obstruction. Nearly anything that produces liver or biliary tract abnormality can affect the bile acid values. Although some conditions produce statistically different degrees of abnormality than other conditions, there is too much overlap when applied to individual patients for the test to be of much help in differential diagnosis. However, there are a few exceptions. Bile acid assay may be useful in the differential diagnosis of congenital defects in bilirubin metabolism (e.g., Gilbert’s syndrome and Dubin-Johnson syndrome;. In neonatal biliary obstruction, there are some reports that oral administration of cholestryamine, an anion exchange resin that binds the bile acids, can aid in differentiating neonatal hepatitis with patent common bile duct from common duct atresia by lowering serum bile acid values if the duct is patent.

In summary, bile acid assay is useful (1) to screen for liver disease when other liver function tests are normal or give equivocal results; (2) in some cases, to help differentiate between hepatic and nonhepatic causes of other liver test abnormalities; (3) in some cases, to follow patients with liver disease when other tests have returned to normal; and (4) to help differentiate certain congenital diseases of bilirubin metabolism.