Test For Liver Disease

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Blood chemistry results can be extremely helpful in zeroing in on medical problems, but they often aren’t clear cut. One of the most common findings is elevation in enzymes that could have come from the liver, but this doesn’t always mean the horse has liver disease.

To help you understand the results from the blood tests your veterinarian ordered, we’ve included a list of liver-related tests commonly found on routine blood chemistry screens and situations where they might be abnormal.

Gamma Glutamyl Transferase (GGT)
This enzyme is the most specific for liver and also the most sensitive. However, GGT may show mild-to-moderate elevations in horses receiving one or more drugs that are processed by the liver without indicating any liver damage per se.

GGT is also commonly mildly to moderately elevated in horses in hard work, especially early in the conditioning period and/or if the horse does not have adequate antioxidant reserves. Low-level toxin exposure (e.g., aflatoxins in grains, a mold toxin) may also rev up GGT activity leading to higher blood levels but without actual damage to the liver.

Horses with poorly controlled Cushing’s disease or insulin resistance may also show mild elevations, probably secondary to oxidative stress and/or impaired energy generation in the liver cells.

To distinguish between those scenarios and liver damage/disease, you need to consider both how high the GGT is, and if other indicators of liver disease are also present. Upper limits of normal for most labs are usually in the range of 40 to 60 IU. Elevations of up to 300 to 400 IU can be seen without changes in any other liver function tests with exercise, drugs, or toxin exposures and don’t necessarily indicate liver damage, although they should prompt a search for the cause. Higher elevations accompanied by abnormal liver-related tests may indicate liver damage.

Alkaline Phosphatase (ALP)
Often called ”alk phos,” this is another enzyme in high concentration in liver, but also in spleen, intestinal tract, bone and lungs. If the elevation is from liver disease, GGT will also be elevated to a similar or greater extent.

ALP is normally elevated in young, growing horses and young horses at some stages of training because it is involved in the formation and remodeling of bone.

Horses on chronic corticosteroids (such as for allergies or lung disease), and horses with high production of cortisol caused by uncontrolled Cushing’s syndrome may also show elevations in ALP since corticosteroids can cause bone resorption. Fractures and inflammatory conditions of bone (e.g., sesamoiditis) may cause mild elevations. A typical upper lab limit for this enzyme is 250 IU.

Aspartate Transaminase (AST)
This is another enzyme widely distributed throughout the body, but in highest levels in liver and muscle. To distinguish between the two, it’s necessary to look for elevations of other enzymes pointing to either muscle (CPK) or liver (GGT and other liver function tests). If only AST and GGT are elevated, this doesn’t distinguish between exercise or liver disease as a cause. Repeat testing, including CPK, should be done close to a bout of exercise to look for abnormal muscle enzymes. Upper limit is around 400 IU.

Alanine Transaminase (ALT)
Elevations in this enzyme are generally more specific for a liver problem than elevations in AST. However, it takes more liver damage to see elevated ALT than elevated GGT, and for this reason GGT is usually a more sensitive test. Expect both of these enzymes to be elevated if there is significant liver disease. Typical upper limit is 25 IU.

Lactic Dehydrogenase (LDH)
This enzyme is present in all body tissues, particularly rich in liver and skeletal muscle. Same precautions for distinguishing between muscle and liver as for AST. Upper limit is around 450 IU.

Bilirubin
Bilirubin is the breakdown product of hemoglobin and myoglobin, the oxygen carrying proteins in the red blood cells and muscle cells. After being stripped of their iron, these proteins are released into the blood as bilirubin. Bilirubin occurs in two forms, conjugated (direct) and unconjugated (indirect). The unconjugated form is the ”raw” bilirubin that is taken up by the liver, processed to conjugated and excreted in the bile. The total bilirubin level in the blood usually runs less than 2.5 mg/dl, with most of this being indirect bilirubin.

Since the liver is the organ responsible for processing bilirubin, elevations are to be expected with liver disease. However, elevations can also occur if the horse is off feed. During fasting, a combination of higher levels of fatty acids released from fat stores for energy and lower liver cellular levels of available glucose seem to combine to reduce how rapidly the liver clears bilirubin. Bilirubin in a fasted horse may reach as high as 10 or 20, and be associated with obvious yellowing of the eyes and gums, without there being any liver disease.

Bilirubin is also commonly elevated for a day or more after strenuous exercise, probably as a combined result of some myoglobin leakage from muscle and exercise related red blood cell destruction. Similarly, it may go up with tying up, other muscle injuries, or anything that causes red blood cell destruction. Again, these elevations in bilirubin are not related to liver disease.

If only elevated bilirubin is found, the cause is not liver disease. As with all other indicators of liver function, elevated bilirubin must be interpreted in the context of all the test results, not as an isolated finding. Because it takes fairly extensive damage to the liver to elevate bilirubin, you would expect to see elevations in all the liver enzymes across the board, including very high levels of GGT.

An exception to this would be a horse whose liver is essentially nonfunctioning and replaced by extensive scarring, in which case enzymes may be very low but bilirubin extremely high. A horse in this condition would also have obvious neurological disease because of back up of other toxin substances in the blood, particularly ammonia. The horse would also have blood-clotting abnormalities.

Albumin
Albumin is an important protein circulating in the blood. Its functions are to bind various drugs and hormones, and to maintain the osmotic pressure of the blood in a normal range. Albumin is manufactured in the liver and levels will drop with severe liver disease, but this would be in a scenario of extensive liver disease as just described under bilirubin. Other causes of low albumin are malnutrition/starvation (low protein intakes) and loss of albumin through intestinal tract disease such as malignancy or colitis.

Albumin may also drop with extensive skin loss (e.g. burns), widespread skin disease such as purpura hemorrhagica, loss in urine with advanced kidney disease or during bodywide bacterial infections. Differentiating between these conditions, all very serious, usually isn’t difficult.