The four main liver enzymes (alkaline phosphatase [ALP], aspartate aminotransferase [AST], ?-glutamyltransferase [GGT], and alanine transaminase [ALT]) can be assessed using a blood chemistry profile. Understanding these enzymes may help determine the cause of liver failure.

Alkaline Phosphatase

ALP is an enzyme in the bile duct cells. The ALP level in plasma increases because of bile duct obstruction, intrahepatic cholestasis, or infiltrative diseases of the liver.⁹ An increase in the ALP level is not specific for liver injury or disease. While ALP is made mostly in the liver, it can also be made in bone, the intestines, and the kidneys. An increase in the ALP level alone is not specific to liver disease. Other causes of increases in the ALP level include bone disease or damage, cancer, and hyperparathyroidism (which affects the blood level of calcium).

Aspartate Aminotransferase

AST is an intracellular enzyme that helps transfer amino groups during conversion from amino acids to ?-oxoacids.⁹ The AST level increases when hepatocytes degenerate or undergo necrosis, after administration of certain medications (e.g., antiseizure drugs), or after traumatic injury (e.g., being struck by an automobile). AST and ALT levels are related to the number of damaged hepatocytes; however, the damage may be reversible.⁹ Like ALT, AST is in other tissues (e.g., muscle, RBCs), so an increase in the AST level does not always indicate liver injury.

?-Glutamyltransferase

GGT, an enzyme found in bile ducts, is usually tested in conjunction with ALP and other liver tests to rule out cholestasis. This combined testing has a higher diagnostic value than any test used alone.⁹

Alanine Transaminase

ALT is an enzyme in hepatocytes. When a hepatocyte is damaged, ALT enters the bloodstream. ALT levels increase dramatically in patients with acute liver disease. Although an elevated ALT level does not necessarily indicate liver damage, the ALT level is more specific for hepatocyte injury than ALP, GGT, or AST.¹¹ A patient can have normal fluctuations in the ALT level throughout the day.¹¹ Certain drugs (e.g., corticosteroids) and hepatic injury (e.g., resulting from being struck by an automobile) can also increase the ALT level.¹¹

Albumin

Albumin, which is synthesized in the liver, is a major protein found in plasma. Albumin is responsible for maintaining colloid osmotic pressure and helping to prevent plasma loss from the capillaries. Patients with chronic liver disease can have decreased albumin levels.¹² By themselves, tests that measure the albumin level cannot determine the degree of liver damage; however, these tests can be used as additional diagnostic tools.

Ammonia

The ammonia level in the blood increases when the liver cannot convert ammonia to urea. An elevated ammonia level may indicate the presence of a liver shunt, hepatitis, or liver failure.¹³

Bilirubin

Bilirubin—a product of hemoglobin breakdown—undergoes conjugation, a process in which the liver makes bilirubin water soluble. In patients with liver damage, conjugation may not occur, causing the total bilirubin level in the blood to increase (hyperbilirubinemia). Total bilirubin—the total amount of bilirubin detected in the blood—includes conjugated and unconjugated bilirubin. Some conditions, such as bile duct obstruction or hemolytic anemia, can increase the total bilirubin level.¹³

The direct bilirubin level reflects only the conjugated portion of bilirubin. If the direct bilirubin level is normal and the total bilirubin level is high, the patient is likely to have excess unconjugated bilirubin (e.g., hemolysis). However, if the direct bilirubin level is high, the patient has excess conjugated bilirubin, potentially signaling the presence of a condition such as neoplasia or gallstones.¹³

Blood Urea Nitrogen

Blood urea nitrogen may be decreased in patients with advanced liver disease because nitrogenous waste products are not being converted to urea.

Serum Protein Electrophoresis

Serum protein electrophoresis is used to measure the levels of various proteins. This test is useful for evaluating patients with abnormal liver enzyme levels because it allows direct quantification of multiple serum proteins, such as total protein, albumin, and ?-, ?-, and ?-globulins. Different liver diseases can cause elevations in different globulins.⁴

Coagulation Testing

It is important not to perform abdominal taps, multiple venipunctures (especially involving the jugular vein), or cystocentesis until a patient’s clotting times are within normal limits.

Prothrombin Time

Prothrombin is an ?-globulin needed for blood coagulation. The prothrombin time (PT) test is performed to assess the extrinsic pathway of the coagulation cascade. Liver disease should be suspected in any patient with a prolonged PT; however, a prolonged PT does not specifically indicate the presence of liver disease, and a normal PT does not indicate the absence of liver disease.

Activated Partial Thromboplastin Time

Thromboplastin is a clotting factor that converts prothrombin into thrombin. The activated partial thromboplastin time test assesses the intrinsic pathway of the coagulation cascade to determine how long it takes a patient’s blood to clot. PT and activated partial thromboplastin time tests are generally conducted at the same time.

Urinalysis

Urinalysis should be conducted to determine whether bilirubin is present in the urine (i.e., bilirubinuria). A trace amount of bilirubin is normal in a concentrated urine sample from a dog, but this finding is abnormal in a cat.¹⁰ If bilirubinuria is evident, additional diagnostic testing should be conducted to rule out liver disease, hemolysis, or other possible causes. 

Imaging

Although some diseases can be ruled out by blood test results, the cause of liver damage cannot usually be determined by blood tests alone. Imaging can be used to reveal tumors, obstructions, or other abnormalities.

Radiography

Radiography is a useful tool but does not usually provide a diagnosis. For example, hepatomegaly can often be observed on a radiograph; however, a tumor originating from the liver can rarely be seen on a radiograph. If neoplasia is suspected, it is important to obtain left, right, and ventrodorsal chest views to look for metastases.

Ultrasonography

Ultrasonography can be used as a diagnostic tool for patients with liver disease. Gallbladder obstructions, tumors, bile duct obstructions, and lipidosis can often be diagnosed using ultrasonography. Ultrasonography can distinguish between solid and fluid-filled masses; however, it cannot yield a definitive diagnosis. It is important that a qualified ultrasonographer conduct the test. For example, finding a liver (portosystemic) shunt in a small puppy can be difficult even for a highly trained individual.

Contrast Angiography

Contrast angiography uses a dye that is usually injected into the jejunal vein.¹⁴ This can be expensive and time-consuming but can definitively diagnose a portosystemic shunt. Angiographic techniques are invasive, requiring a specially trained veterinarian. Patients undergoing angiography require general anesthesia. Because of the expense and time associated with angiography, most veterinarians prefer exploratory surgery instead.

Computed Tomography

While computed tomography (CT) is not as readily available as other imaging diagnostics, it does allow for quick scans of the liver before and after contrast is administered. CT can identify hepatic nodules that cannot be detected by ultrasonography. CT can also help diagnose portosystemic shunts. The disadvantages of CT are high cost, poor availability, and the need for general anesthesia.¹⁵

Magnetic Resonance Imaging

As with CT, magnetic resonance imaging (MRI) can identify hepatic nodules that cannot be detected by ultrasonography. MRI also offers excellent anatomic detail of the liver. As with CT, the disadvantages of MRI are high cost, poor availability, and the need for general anesthesia.¹⁵

Biopsy

Fine-Needle Aspiration

Ultrasound-guided fine-needle aspiration biopsy can be very useful for diagnosing liver disease; however, this test has an increased risk of complications because patients with liver disease may have clotting abnormalities and may hemorrhage. Fine-needle aspiration biopsy can also be performed “blindly,” without ultrasonography, but samples obtained in this manner are often of poor diagnostic quality.

Because the liver plays a role in the coagulation cascade, it is important to rule out clotting problems before a biopsy. Little or no sedation is generally needed to perform a needle biopsy; however, patient movement may result in liver laceration and/or retrieval of an inadequate sample. Certain diseases or types of neoplasia can be diagnosed using this method; however, the sample obtained does not always yield a diagnosis.

Percutaneous-Needle Aspiration

Ultrasound-guided percutaneous-needle aspiration can also be used to obtain a biopsy sample. Although the needle used can obtain a larger sample than a fine needle, the sample can also be nondiagnostic.

Laparoscopic Biopsy

Compared with needle biopsy, laparoscopic biopsy can be used to obtain a larger sample of the affected area of the liver, and the laparoscope provides a better view of the liver than does ultrasound imaging. Laparoscopic biopsy is more invasive than ultrasound-guided fine-needle aspiration; therefore, patients undergoing the former require general anesthesia. As with needle biopsy, it is important to ensure that a patient does not have a clotting problem before laparoscopic biopsy.

Once a diagnosis has been made, a treatment plan should be formulated. Because many treatment options are available for patients with liver disease, it is important that clients be informed of, and understand, these options. Even if the patient’s prognosis is good, some clients may decide to forgo treatment because it can be expensive and time-consuming; other clients may choose to euthanize their pet if it requires long-term care or extended hospitalization.

The overall treatment goal for a patient with liver disease is to use a specific treatment, when possible, and provide supportive care. During treatment, it is important to manage complications associated with liver failure, such as gastrointestinal ulceration, anemia, infection, ascites, edema, and coagulopathy.¹⁰ Treatment varies according to the identified cause of the disease.

When caring for a patient with liver disease, the technician should frequently monitor all vital systems (e.g., cardiovascular, respiratory, neurologic). Because the technician likely spends the most time with the patient, he or she can alert the veterinarian to early signs of complications. It is important for the technician to thoroughly evaluate the patient during monitoring. For example, if the color of a patient’s mucous membranes is not checked regularly, the technician may not recognize that anemia has developed. In addition, the color of a jaundiced patient can change hourly, so it is important to notify the veterinarian if a change occurs.

Aggressive fluid therapy is one of the most important treatment options when managing a patient with liver disease. By returning perfusion parameters to normal, fluid therapy can help to improve hepatic circulation and prevent complications such as disseminated intravascular coagulation, shock, or renal failure.¹⁰ Often, 0.45% sodium chloride is used to help prevent sodium retention and portal hypertension.¹⁰ Colloids such as hetastarch may be used to help restore oncotic pressure. Electrolyte levels should be monitored, and fluid adjustments should be made accordingly. Ascites may need to be drained to increase comfort and ease breathing.

Proper nutrition is essential for patients being treated for liver disease. During the initial treatment stages, patients that appear nauseous or are vomiting should not be fed by mouth. However, nutritional needs must be considered in patients that require long-term care. A feeding tube may be placed if a patient is unwilling to eat.¹³ A feeding tube allows controlled, effective feeding compared with force-feeding using a syringe. Technicians can encourage the patient to eat by offering a variety of foods or by hand-feeding. Because patients with certain liver diseases require special diets, the veterinarian should be consulted before feedings are initiated. In patients with diseases such as feline hepatic lipidosis, nutrition plays a crucial role in recovery.¹⁰

Several hepatosupportive agents may be used to help control chronic liver problems in some pets, and the use of these agents to control acute liver failure has become more common. Most of these agents are nutraceuticals that are antioxidants.¹⁶ Antioxidants that are considered hepatosupportive are vitamin E, S-adenosylmethionine, silymarin, phosphatidylcholine, vitamin C, and N-acetylcysteine.¹⁶ Ursodeoxycholic acid is also considered hepatosupportive.¹⁶ Because hepatosupportive agents do not cure severe disease but may improve the health of the liver, they should be used in conjunction with other treatments.¹⁶S-Adenosylmethionine—one of the most commonly used agents—has been shown to help improve liver function and appears to have no adverse effects.¹⁶ It is commonly used in people to help protect against alcoholic hepatitis.¹⁶ Denamarin (Nutramax Laboratories)—a newer supplement for dogs and cats—contains S-adenosylmethionine and silybin. Silybin is the most active fraction derived from milk thistle, which has been used to help support liver function.¹⁶

Additional treatments may be necessary to address complications associated with liver disease. For example, mannitol and furosemide may be used to help reduce cerebral edema, which may develop in patients with severe liver disease. Technicians should immediately notify the veterinarian of anisocoria or changes in neurologic status. If a patient develops a coagulopathy, fresh frozen plasma may be given. A technician may be the first to notice petechiae on a patient. 

Follow-Up

Often, patients are discharged from the hospital even though they remain slightly jaundiced or have elevated levels of liver enzymes. In some cases, it may take months for a patient’s liver to fully recover; therefore, rechecking blood work and/or performing ultrasonography can help monitor response to treatment. Occasionally, a patient may be readmitted to the hospital if its condition worsens. Technicians should educate owners about signs that a pet’s condition has worsened; for example, owners can be taught to look for signs of jaundice by checking the color of the patient’s mucous membranes and sclera. If the pet becomes lethargic, develops anorexia, begins vomiting, develops diarrhea, or exhibits worsening jaundice, the owner should ensure that the pet receives immediate medical attention. 

Prognosis

Depending on the underlying cause of liver disease, some patients may recover quickly. Within 24 hours, a patient’s condition can change drastically—a patient that is very jaundiced and lethargic can become alert and exhibit no jaundice. However, some patients experience severe complications from liver disease, potentially resulting in a wide variety of sequelae.

Patients with acute liver failure generally have a good prognosis if the disease is diagnosed early and treatment is started immediately.¹⁰ However, patients with chronic liver disease have a variable prognosis. Patients with neoplasia may have a favorable outcome if complete resection is possible and chemotherapy is started early. However, the prognosis is guarded in most patients with hepatic neoplasia.¹⁰