The Top Causes of Elevated Liver Enzymes In Dogs

It goes something like this: You have blood work done on your dog, and your vet reports that the liver enzymes are elevated. This can be concerning for dog owners, but what does this mean, and do you need to be concerned? It is important to understand that elevated liver enzymes do not necessarily indicate the presence of liver disease, but rather signal that changes are occurring within the liver.

The liver is a vital organ that is responsible for various metabolic functions, such as detoxification and protein synthesis, among others. When the liver is affected, the activity of the liver enzymes increases and this is what results in elevated values in the blood. In this article, I will review the many potential causes of elevated liver enzymes in dogs, from benign to more severe causes.

What are liver enzymes?

Liver enzymes are proteins that are produced in the liver that help to metabolize proteins, fats and carbohydrates. The liver is the major organ that is involved in detoxifying drugs, metabolites, and toxins.

In dogs, the most commonly measured liver enzymes in blood tests are alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP).

These enzymes (ALT and AST) are present within the liver cells, and their numbers will often increase when there is damage or inflammation in the liver itself. Interestingly, AST is also found in skeletal muscle, and ALP is also found in bones. Therefore, the increase of either of these enzymes could suggest changes in organs other than the liver.

If your dog has an elevated ALP level, this could indicate liver damage or disease, but also bone growth in puppies, as well as increases secondary to medications such as prednisone and phenobarbital.

What causes elevated liver enzymes in dogs?

There are many reasons for high liver enzymes in dogs. When I see a dog that has elevated liver enzymes, I will separate the possible causes into two categories: hepatic (primary) and extrahepatic. This means inside or outside the liver, respectively.

Primary causes of elevated liver enzymes in dogs

Primary hepatic causes of high liver enzymes in dogs refer to conditions that result in liver changes, with or without disease. The end result are increases in liver enzymes in the blood.

Here is a list of possible causes:

• Hepatitis: Hepatitis refers to inflammation of the liver and can be caused by viral, bacterial, or inflammatory factors.
• Benign nodular hyperplasia: Benign nodular hyperplasia is a condition commonly seen in older dogs in which the liver develops multiple small non-cancerous nodules.
• Drug-induced: Some drugs, such as steroids (e.g. prednisone) and phenobarbital, can cause elevated liver enzymes in dogs, especially ALP.
• Congenital liver diseases: Certain liver diseases, such as portosystemic liver shunts and copper storage diseases, are genetic and can cause liver enzyme levels to increase.
• Toxins: Some toxins can induce the activity of liver enzymes in dogs. These can include xylitol, aflatoxins, and lead toxicity, for example.
• Cholangitis: Cholangitis refers to inflammation of the bile ducts that carry bile from the liver to the small intestine. It can cause liver damage and elevated liver enzymes.
• Cirrhosis: Cirrhosis is a chronic, end-stage liver disease that leads to scarring and permanent damage to the liver. It can be caused by chronic infections, exposure to toxins, or chronic active hepatitis.
• Liver cancer: Diffuse cancer in the liver, whether malignant or benign, can cause liver enzyme levels to increase. Common cancers that can affect the liver include lymphoma, carcinoma, and hemangiosarcoma.

Secondary causes of elevated liver enzymes in dogs

Secondary, or extrahepatic causes of elevated liver enzymes in dogs refer to conditions that occur outside of the liver, yet will influence the liver.

Here are some common extrahepatic causes of elevated liver enzymes in dogs:

• Pancreatitis: Pancreatitis is inflammation of the pancreas and can cause liver enzyme levels to rise due to inflammation spreading to the liver.
• Diabetes: Dogs with diabetes can have elevated liver enzymes due to the negative metabolic state (subclinical hepatic lipidosis).
• Cushing's disease: Dogs with Cushing's disease, or hyperadrenocorticism, can have elevated liver enzymes due to excess steroid production, leading to swelling of the liver.
• Heart disease: Right-sided heart disease can cause liver congestion, leading to elevated liver enzyme levels.
• Inflammatory bowel disease: Inflammatory bowel disease (IBD) can cause elevated liver enzyme levels due to inflammation in the gastrointestinal tract.

These illnesses can lead to a benign reactive/vacuolar hepatopathy, causing an increase in liver enzymes, but normally, there is no impact on how the liver functions.

How to determine if your dog’s elevated liver enzymes are of concern

If your vet tells you that your dog has elevated liver enzymes and is not on any medications that would cause the elevations, such as prednisone or phenobarbital, nor does your dog have Cushing's disease that would explain the increases, here are some options that I would recommend to consider:

• Liver function test: A bile acid blood test can evaluate liver function and performance. If they are high, it suggests liver impairment.
• Medication trial: Antioxidants like SAMe or medications like ursodiol can support liver health. I then recommend rechecking the liver enzymes in 30 days after starting these medications.
• Recheck: If your dog is symptom-free, rechecking levels in a few months might be suggested.
• Imaging: X-rays or ultrasound can assess the liver for evidence of infection, inflammation, or tumours.
• Liver biopsy: In severe cases, a biopsy may be recommended for further analysis.

Do all elevated liver enzymes need to be investigated further?

Elevated liver enzymes in dogs do not always need to be investigated further. In mildly increased liver enzymes, I usually recommend periodic blood testing to start trending the values before starting further testing.

With that being said, liver enzyme values greater than 2-3 times the upper limit of normal should be evaluated as they can indicate more serious conditions. This is also assuming your dog is asymptomatic, and there are no abnormalities on its physical exam.

Medications such as corticosteroids (prednisone) and phenobarbital will predictably cause elevated liver enzymes in dogs, especially the ALP. In these cases, the elevated liver enzyme values are not indicative of liver disease and will usually resolve with the discontinuation of the medication.

Additionally, puppies with an elevated ALP enzyme are usually not concerning, as this could be due to skeletal growth and development. If other liver enzymes are increased as well as the ALP, then I would investigate further, as it would then be less likely due to bone growth alone.

Finally, elevated liver enzymes in dogs can be observed as part of an aging process, as normal age-related changes occur to cause increased activity of certain enzymes. Examples include nodular and vacuolar hepatopathy. In this case, I usually recommend periodic blood testing every 4-6 months.

Elevated liver enzymes in dogs can be caused by a variety of conditions, both within and outside the liver. The most common causes of elevated liver enzymes in dogs are due to medications like prednisone, Cushing's disease, liver inflammation such as hepatitis, and benign, age-related changes.

In mild cases of elevated liver enzymes, periodic blood testing may be all that is needed to ensure there are no more serious underlying issues. However, if your dog’s elevated enzyme levels persist or become particularly high (greater than 2-3 times the upper limit of normal), further investigation should be done as soon as possible.

If your dog has trending liver values where they are increasing, and there are other symptoms such as increased thirst, changes to appetite, vomiting or diarrhea, etc., I would recommend discussing with your veterinarian the next steps to determine the cause.