When Your Dog Has Abnormal Liver Enzymes
What's a veterinarian to do when a pet that appears to be happy and healthy has abnormal liver enzymes?
While the very purpose of testing the liver enzymes is early recognition of problems to provide opportunities for earlier and more meaningful intervention, the veterinary practitioner is challenged to determine if the abnormal result really does constitute a problem. Veterinary internists are often asked to consult about middle aged to older dogs that have moderately elevated serum levels of alkaline phosphatase (ALK, ALP, SAP), a commonly measured liver enzyme.
If pets appear otherwise well, it is exceedingly important to verify the abnormal result before pursuing it as a potential problem. In other words, the veterinarian will need to make sure that the abnormality shows up on re-tests and not just a fluke. Repeating the lab test in one to two weeks with ideal patient preparation is common. Once the abnormality is verified, the veterinarian can try to determine whether the patient's health is in danger.
While alkaline phosphatase is produced primarily in the liver, there are other tissue sources of the enzyme. In a healthy animal, the intestinal tract, the kidneys, placenta, and bone all produce variable amounts of ALP. The form of the enzyme differs with the tissue of origin and the life span varies accordingly. In the dog, the ALP produced in the placenta and kidneys circulates in the blood stream for only a few minutes, so it is rare to see significant elevations in the bloodstream.
Thus, the veterinarian may be concerned when there are such elevations. The form of alkaline phosphatase that is induced by corticosteroids, and those forms that occur secondary to liver disease or bone damage, circulate for about 72 hours. Elevations in the bone fraction of ALP are very common in puppies that have not yet reached skeletal maturity because of ongoing bone growth; such elevations also occur often in adults that have bone tumors or infection.
In most cases, the veterinarian is relying on the ALP tests to provide evidence about the health of the liver. However, the test offers little or no information about how well the liver is functioning -- that is, whether the liver is able to do its job of detoxifying the blood and metabolizing and excreting wastes and by products. Some confusion may arise because the medical community has traditionally referred to liver enzymes as LFTs or liver function tests, a term that pops up frequently on television medical dramas. But in dogs and cats, the liver enzymes correlate poorly with the liver's functional capability.
The magnitude of any increase in the ALP can, however, be suggestive of the extent of the liver damage. Generally, the higher the level of ALP, the greater the doctor's concern. But since many labs use different reference standards, it's common to discuss the liver values in terms of how many times normal they are. This allows veterinarians to compare values measured by different laboratories.
Any primary liver or gall bladder disease that disturbs the gross or microscopic circulation of bile will likely raise the serum ALP. Hepatitis or liver inflammation, cancer, cirrhosis, degenerative processes or toxic changes are commonly associated with elevations in ALP. Pancreatic disorders, gall stones, and other diseases of the biliary tree behave similarly. Frequently other liver enzymes will be elevated concurrently, such as alanine transferase (ALT) and gamma-glutamyl transpeptidase (GGT).
The reason why dogs that have abnormal liver enzymes usually appear to be in normal condition is that many liver diseases won't be apparent until liver function is disturbed or global changes occur. Dogs with important hepatobiliary disease can, then, appear healthy.
Processes or diseases outside the liver, such as diabetes mellitus or blood borne infection, frequently impact the liver, causing secondary or reactive changes in the liver tissues. Reactive hepatopathies can mimic primary liver disease and may mislead the veterinary diagnostician. Many patients with primary or secondary liver disease will have elevated levels of liver and corticosteroid-induced ALP. Comprehensive laboratory screening and x-rays are often needed to aid the veterinarian in discriminating between primary and secondary liver disease.
The history plays an equally important role, especially whether the pet is on any medications. Regular use of anticonvulsants, such as phenobarbital or recent administration of prednisone, dexamethasone or other corticosteroids may elevate the serum ALP to 20-30 times normal. This response is recognized in the majority of patients receiving such medications, but may occur subsequent to any medication as an unexplained or idiosyncratic reaction. Veterinarians will scrutinize the history for any signs suggesting hyperadrenocorticism, such as increased thirst and urination, panting, weight gain or diminished activity, and all results of excessive blood levels of corticosteroids.
Patients with early hyperadrenocorticism or Cushing's disease may have few signs of the disease, so special endocrine diagnostics may be ordered to aid in the investigation of ALP increases. Unfortunately, endocrine tests are well known for producing equivocal or gray test results. There is no single test that can verify or refute a diagnosis of Cushing's disease, so owners are encouraged early on to have patience with the diagnostic process.
When the veterinarian is satisfied that there are no important extrahepatic diseases and there is insufficient evidence of Cushing's disease, the focus returns to the liver. Abdominal x-rays give meaningful information about liver size and shape, but nothing about the liver's architecture. For this we rely on abdominal sonography. Ultrasound studies of the liver can locate focal lesions or detect diffuse changes throughout the organ. Gallstones, pancreatic changes, and other disturbances to bile flow may be confidently diagnosed with a careful ultrasound study. The test is not perfect, however, and cannot be used to rule out hepatitis or other infiltrative diseases. But if the liver is relatively normal in size, shape and architecture, can a liver biopsy be justified? The relative costs and risks of liver biopsy must be weighed for the individual patient. Detection of liver dysfunction with a noninvasive blood test such as a bile acid assay usually justifies the procedure.
Ultimately, however, some sampling of the liver is needed to document the microscopic changes and to rule out occult liver disease. Happy dogs with no clinical signs of illness are likely to have a cellular diagnosis of vacuolar hepatopathy. These changes are usually idiopathic or unexplained if there is no history of medication use and no evidence of Cushing's disease. Corticosteroid induced alkaline phosphatase is responsible for the increase in the blood levels of ALP; possibly, there is some chemical signal for the liver cells to change structurally, but the trigger is not known.
Vacuolar hepatopathy is not highly pathologic and does not appear to warrant any specific treatment or change in patient management. Special liver friendly diets are suggested by some veterinarians, but may not be needed if liver function remains normal over time. If liver function deteriorates, then it's likely that the patient has a different liver condition.
Occasionally, dogs will develop clinical signs and laboratory evidence of hyperadrenocorticism months to years later, so pet owners must be vigilant in their observation for signs of illness or abnormality if tests show abnormal liver enzymes. Appropriate diagnostics are likely to be repeated at that time. It may be, also, that some patients diagnosed with idiopathic vacuolar hepatopathy by needle biopsy have nodular hyperplasia, a degenerative process of the liver that does not pose an important health issue.
The good news is that a diagnosis of idiopathic vacuolar hepatopathy means your happy dog is probably really that: a happy, healthy dog. Unfortunately, verifying the good news and ruling out the other more serious conditions that raise alkaline phosphatase may be somewhat costly and require invasive diagnostics, such as liver biopsy.
March 12, 2006
Written by: Celeste A. Clements, DVM, Diplomate ACVIM