Clinical Approach to Elevated Liver Enzyme Activities

Emergency Veterinarian TorontoInternal Medicine Clinical Update:
Clinical Approach to Elevated Liver Enzymes
Michael Goldstein, DVM, Diplomate ACVIM
Central Toronto Veterinary Referral/Emergency Clinic

Elevated liver enzymes are a common finding noted in blood work performed on both healthy and ill dogs and cats. One study documented elevated alkaline phosphatase (ALP) concentrations in up to 40% of dogs with elevated liver enzymes. However, the finding of elevated liver enzymes does not always mean that there is significant primary liver disease. Therefore, as clinicians we must evaluate the history and undertake physical examination (PE) to determine the significance of the elevation in order to determine a diagnosis and create a treatment plan.

There are two major categories to classify liver enzymes: hepatocellular leakage (Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST)) and cholestatic/induction enzymes (ALP and Gamma-Glutamyltransferase (GGT)).

ALT is primarily located in the cytoplasm of the liver cells, whereas AST is found in abundance in a variety of tissues, most notably skeletal muscles. Both of these aminotransferases rapidly leak out of the hepatocyte when there is altered permeability from injury or metabolic disturbance. The magnitude of elevation correlates with the number of hepatocytes involved but does not reflect the overall functional capacity of the liver. This vital organ has an immense reserve capacity and as such animals with marked enzyme elevations may still have enough liver function to prevent clinical disease from becoming apparent.

ALP and GGT are membrane-bound enzymes and need to be cleaved from the membrane before becoming elevated in the blood. As such, there can be a delay between elevation in the aminotransferases and cholestatic/induction enzymes. There are multiple forms of ALP but the most clinically significant forms are bone (B-ALP), liver (L-ALP), and glucocorticoid (G-ALP). The G-ALP has little to no effect in cats but in conjunction with the L-ALP has been found to be associated with hepatobiliary disease, endocrine disorders, and pancreatitis in dogs. GGT is more sensitive but less specific than ALP in cats for hepatobiliary disease. I often use GGT when attempting to determine the cause of hepatic lipidosis in cats, since an elevated ALP and normal GGT concentration is consistent with primary hepatic lipidosis.

My general rules of interpretation of liver enzymes:

  1. 2-3 fold increases in ALT/AST concentration in healthy pets
    1. Revisit patient history, drugs, supplements, etc.
    2. Recheck in 2 to 3 weeks


  1. 3 fold increases in ALT/AST, history, and PE suggest a problem
    1. Liver function tests pre- and post-prandial bile acids
    2. If bile acids are abnormal then ultrasound and possible liver biopsy


  1. The degree of elevation in the ALP does not correspond to the degree of illness


  1. If a patient has no clinical signs and only an ALP elevation then it does not need to be evaluated for Cushing’s disease

CTVRC_Elevated liver enzymesIf you have questions regarding liver disease or any Internal Medicine cases please do not hesitate to contact Dr. Michael Goldstein, Dr. Stephen Kruth or Dr. Kimberly Ho for a free, no obligation phone consultation at 416-784-4444 ext 1 and follow the prompts.

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