Cases of equine hepatic disease (Proceedings)
The problem oriented approach to liver disease involves identification of liver disease as a differential diagnosis for several problems. In this discussion, we will discuss liver disease as a differential diagnosis for: icterus, increased liver enzymes, neurologic disease, fever ± colic, and weight loss. It is important in most cases whether the problem results from liver disease alone or liver disease with liver failure.
Icterus in horses can occur as a result of normal digestion of carotene pigments in grass and hay, fasting and anorexia (partial or complete), liver failure, or hemolysis. Forage consumption normally causes mild yellow discoloration of the sclera, plasma or serum, and tissues. For this reason, the "icterus" index in horses does not always correlate with plasma or serum bilirubin concentration. That is the sclera and membranes can be yellow with a normal bilirubin. Measurement of the total bilirubin concentration differentiates this situation simply.
Fasting hyperbilirubinemia results in elevations of total bilirubin concentration in horses without liver disease. It appears that bilirubin uptake into hepatocytes in horses is dependent on eating. It is possible that production of the protein responsible for bilirubin uptake (ligandin) is stimulated by eating. Dramatic elevations of indirect bilirubin (up to 15 mg/dl) can result from fasting. The key is that the direct (conjugated bilirubin) remains completely within the reference range (usually less than 1 mg/dl) during fasting or anorexia. Hepatic enzymes (gamma glutamyl transferase, aminoaspartase transferase, and sorbitol dehydrogenase) and bile acids remain normal during fasting.When icterus is due to elevations of bilirubin due to hepatic failure, direct and indirect bilirubin are elevated thereby elevating total bilirubin, bile acids, and liver enzymes. The gamma glutamyl transferase (GGT) is an induction enzyme produced during dilation of the biliary tree. However, it is a sensitive indicator of any liver disease in the horse since hepatocyte swelling blocks canaliculi between cells causing biliary stasis and GGT production. Aspartate aminotransferase (AST) is leaked form hepatocytes during hepatocyte damage but is also an indicator of muscle damage. Alanine aminotransferase (ALT) does not leak appreciably from equine hepatocytes so this enzyme used in assessment of liver disease in small animals is not useful in horses. LDH is very nonspecific and not helpful in assessment of liver disease in horses. Sorbitol dehydrogenase is a specific indicator of hepatocyte damage but is labile requiring rapid delivery to the laboratory after collection. Bile acids can be assessed in horses by laboratories that measure total bile acids. Sample can be collected at any time before or after eating. Elevations up to 20 mmol/liter can occur in anorexic horses with other system disease. Elevations over 20 mmol/liter sensitively indicate hepatic failure.
Icterus due to hemolysis is generally accompanied by a drop in packed cell volume and red blood cell count. Liver enzymes and bile acids will commonly remain normal in these cases. Elevations of unconjugated bilirubin are most dramatic but concurrent elevations in conjugated bilirubin are not uncommon in horses with hemolysis.
In summary, laboratory evaluation of horses with icterus includes bilirubin (direct and indirect, GGT, AST (Never ALT or LDH) or SDH, OCT, PCV, and bile acids. An example occurred in an eight-year-old Tennessee Walking horse that developed icterus and limb swelling acutely while in the recovering stages of Streptococcus zooepidemicus induced pneumonia. Laboratory changes occurred as follows:
• GGT 21 (normal less than 32)
• AST 200 (normal less than 179)
• Bilirubin 7.2 mg/dl with direct 3.1
• Bile acids 12
• PCV 18
• Negative Coggins
This Tennessee Walking horse responded favorably to conservative management.
Another common scenario related to laboratory changes associated with the liver is when elevations in liver enzymes occur while performing screening blood work and signs compatible with liver answer disease are absent. Common examples occur during prepurchase examinations and elevations of GGT may occur without clinical disease. Elevations in GGT can occur nonspecifically in response to other disease resulting in liver perfusion changes and drug administration. However, elevations in GGT without clinical disease can also be and early indicator of bacterial cholangitis or chronic active hepatitis so should not be ignored. These laboratory changes are best handled by rechecking serum chemistry enzymes in 30 days. In most cases, transient elevations have resolved and persistent elevations are due to liver disease. If elevations persist beyond 6 to 8 weeks, liver ultrasound and liver biopsy are indicated.