Serum Bile Acids

Reference Intervals

Canine	Interval
Preprandial (fasting 8 to 12 hours)	≤ 6.0 μmol/L
Postprandial (2 hours)	≤ 13.5 μmol/L
Feline	Interval
Preprandial (fasting 8 to 12 hours)	≤ 6.0 μmol/L
Postprandial (2 hours)	≤ 10.0 μmol/L

Sample Requirements & Shipping Information

• 0.2 mL of serum (non-hemolytic, non-lipemic).
• Please clearly label preprandial and postprandial samples.

Turnaround

• 3-5 business days after receipt of samples.

Interpretation

Canine	Interpretation
Preprandial concentration
≤ 6.0 µmol/L	Result is within the reference interval. Liver disease is not ruled out.
6.1 to 14.9 µmol/L	Mildly increased preprandial bile acid concentration. Result is usually not clinically significant.
≥ 15.0 µmol/L	Increased preprandial total serum bile acids concentration. Suggests, but does not conclusively prove, significant hepatobiliary dysfunction or abnormal hepatic perfusion. Consider further diagnostic tests for liver disease. Increased preprandial total serum bile acids concentration. Suggests, but does not conclusively prove, significant hepatobiliary dysfunction or abnormal hepatic perfusion. Consider further diagnostic tests for liver disease.
Postprandial concentration
≤ 13.5 µmol/L	Result is within the reference interval. Liver disease is not ruled out.
13.6 to 29.9 µmol/L	Mildly increased postprandial bile acid concentration. Result is usually not clinically significant.
≥ 30 µmol/L	Increased postprandial total serum bile acids concentration. Suggests, but does not conclusively prove, significant hepatobiliary dysfunction or abnormal hepatic perfusion. Suggests, but does not conclusively prove, significant hepatobiliary dysfunction or abnormal hepatic perfusion. Consider further diagnostic tests for liver disease.

Feline	Interpretation
Preprandial concentration
≤ 6.0 µmol/L	Result is within the reference interval. Liver disease is not ruled out.
6.1 to 14.9 µmol/L	Mildly increased preprandial bile acid concentration. Result is usually not clinically significant.
≥ 15.0 µmol/L	Increased preprandial total serum bile acids concentration. Suggests, but does not conclusively prove, significant hepatobiliary dysfunction or abnormal hepatic perfusion. Consider further diagnostic tests for liver disease. Increased preprandial total serum bile acids concentration. Suggests, but does not conclusively prove, significant hepatobiliary dysfunction or abnormal hepatic perfusion. Consider further diagnostic tests for liver disease.
Postprandial concentration
≤ 10.0 µmol/L	Result is within the reference interval. Liver disease is not ruled out.
10.1 to 29.9 µmol/L	Mildly increased postprandial bile acid concentration. Result is usually not clinically significant.
≥ 30 µmol/L	Increased postprandial total serum bile acids concentration. Suggests, but does not conclusively prove, significant hepatobiliary dysfunction or abnormal hepatic perfusion. Suggests, but does not conclusively prove, significant hepatobiliary dysfunction or abnormal hepatic perfusion. Consider further diagnostic tests for liver disease.

Moderately to markedly increased serum bile acid concentrations are indicative of significant hepatobiliary dysfunction, cholestasis, or portosystemic shunting (congenital or acquired). But they are not specific for any liver disease and in the absence of portosystemic shunting dogs and cats with liver disease often have normal serum bile acid concentrations.

It is important to note that fasting serum bile acid concentrations may be slightly higher than the upper limit of the reference interval or higher than the postprandial value due to spontaneous contraction of the gall bladder in the fasting state, or due to delayed gastric emptying. Mildly increased preprandial and postprandial serum bile acids concentrations can also be the result of increased bacterial deconjugation of primary bile acids into secondary bile acids (which are more efficiently absorbed).

False negative results may occur if enterohepatic circulation of bile acids does not occur due to lack of gall bladder contraction. This could be a problem if a patient is anorectic, does not eat enough food, consumes a diet with insufficient protein or fat, vomits the test meal, or has delayed gastric emptying.

Measurement of serum bile acids in a patient with proven cholestasis is of no clinical benefit. Additionally, there is usually no utility in measuring serum bile acid concentrations in patients with hyperbilirubinemia.

General Information

Bile acids are synthesized in the liver from cholesterol. Bile acids that are produced by the hepatocytes are conjugated to an amino acid. In both dogs and cats, conjugation is primarily to taurine, but dogs may also convert to a conjugation with glycine. The conjugated bile acids produced by the liver are called primary bile acids. These are secreted in the bile and then stored in the gall bladder. When the gall bladder contracts the bile acids are released into the intestines. Spontaneous gall bladder contraction also occurs during the interdigestive phase (resulting in higher fasting bile acid concentrations than post-prandial). Bile acids act as ionic detergents, aiding the emulsification of dietary lipids and their subsequent intestinal absorption in micelles as well as having a newly appreciated role in cell signaling.

Hepatobiliary disease can cause increased serum bile acid concentrations by interfering with hepatocellular function, by causing decreased bile flow (cholestasis), or by altering the hepatoportal blood flow. The main clinical use of serum bile acid measurement is to assess hepatic function in patients suspected to have hepatic disease, with serum bilirubin concentrations that are within the reference interval. Measurement of postprandial serum bile acid concentration does not seem to have an advantage over fasting serum bile acid concentrations or vice versa. Sensitivity can be increased by collecting paired preprandial and two-hour postprandial samples. Numerous studies have shown that serum bile acid measurement is a useful test for diagnosing portosystemic shunting (congenital or acquired) in dogs and cats. One study found the sensitivity of fasting serum bile acid measurement for diagnosing portosystemic shunts to be 93% for dogs and 100% for cats. However, the sensitivity of serum bile acid measurement for detecting hepatic insufficiency is lower than for detecting portosystemic shunting.

Further reading

1. Lidbury JA, Steiner JM. Diagnostic evaluation of the liver. Chapter 61. In Gastrointestinal and Liver Diseases of the Dog and Cat. 1st edition. Eds. Washabau, Rand, Hall EJ. Saunders 2012 863–875.
2. Center SA, Manwarren T, Slater MR et al. Evaluation of twelve-hour preprandial and two-hour postprandial serum bile acids concentrations for diagnosis of hepatobiliary disease in dogs. Journal of the American Veterinary Medical Association 1991;199:217-226.
3. Center SA, Baldwin BH, Erb HN et al. Bile acid concentrations in the diagnosis of hepatobiliary disease in the dog. Journal of the American Veterinary Medical Association 1985;187:935-940.
4. Center SA, Erb HN, Joseph SA. Measurement of serum bile-acids concentrations for diagnosis of hepatobiliary disease in cats. Journal of the American Veterinary Medical Association 1995;207:1048-1054.
5. Gerritzen-Bruning MJ, van den Ingh TS, Rothuizen J. Diagnostic value of fasting plasma ammonia and bile acid concentrations in the identification of portosystemic shunting in dogs. Journal of Veterinary Internal Medicine 2006;20:13-19.
6. Melgarejo T, Williams DA, O’Connell NC et al. Serum unconjugated bile acids as a test for intestinal bacterial overgrowth in dogs. Digestive Disease Science 2000;45:407-414.