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Abnormal liver enzymes: A practical clinical approach (Proceedings)

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Apr 01, 2009

The detection of abnormal liver biochemical tests in the asymptomatic as well as the symptomatic patient is a common finding on the routine blood screen. In humans it is reported that up to 4% of asymptomatic persons have increased serum liver enzymes. In a study of 1,022 blood samples taken from both healthy and sick dogs and cats 39% had ALP increases and 17% had ALT increases. The identification of liver biochemical abnormalities should suggest certain diagnostic possibilities and should guide a protocol for further investigation. Liver biochemical abnormalities are often nonspecific; the measured enzymes can be isoenzymes from another tissue or the same enzyme from a different tissue source. An understanding of the liver biochemical tests is essential when evaluating the patient in question. Liver biochemical test abnormalities are categorized into groups that reflect 1) hepatocellular injury, 2) cholestasis or 3) tests of impaired metabolic function or synthetic capacity.

Laboratory Tests

It is important to understand basic liver related laboratory tests in order to determine the possible etiologies for abnormal levels and to develop a course of action. Many liver tests are not specific only to the liver but can be abnormal from primary non-hepatic disease as well. Evaluation of liver biochemical tests must be interpreted in light of the history, medications and clinical findings. The magnitude and duration of increase is also dependent on the type, severity and duration of the stimulus and the species. They do not prognosticate the irreversibility of liver disease at one point in time. Also because the liver is involved in so many functions no single laboratory test in this category reflects the complete functional state of the liver.

Indicators of Hepatocellular Injury

A common presentation is the isolated increase in either alanine aminotransferase (ALT) or aspartate aminotransferase activity (AST). Canine and feline hepatocyte cytoplasm is rich in ALT and contains lesser amounts of AST. Altered permeability of the hepatocellular membrane caused by injury or a metabolic disturbance results in a release of this soluble enzyme. Conceptually ALT and AST should be thought of as hepatocellular "leakage "enzymes. Subsequent to an acute, diffuse injury, the magnitude of increase crudely reflects the number of affected hepatocytes. It is however neither specific for the cause of liver disease or predictive of the outcome. The plasma half-life of ALT activity is 2.5 days and AST about 1 day, however ALT concentrations may take many days to decrease following an acute insult. Persistent increases of only ALT are characteristic of chronic hepatitis in the dog.

Specific Evaluation of Increased ALT

Persistent ALT increases should be investigated when they are greater than twice normal. The most important diagnosis to make is chronic hepatitis. Early diagnosis and prompt therapy improves patient survival. Hepatitis often begins in dogs 2-5 years of age with only ALT increases. Females are over-represented and breed associated hepatitis is well known. Dogs with significant hepatitis usually also have concurrent bile acid abnormalities. ALT elevations in young dogs under 1 year of age is sometimes associated with portal vascular anomalies and bile acid concentrations should be obtained to exclude that possibility. Occasionally I see young dogs evaluated prior to elective surgery having unexplained ALT increases for unknown reason that correct over time.

A variety of tissues, notably skeletal muscle and liver, contain high aspartate aminotransferase activity (AST). Hepatic AST is located predominately in hepatocyte mitochondria (80%) but also soluble in the cytoplasm. Skeletal muscle inflammation invariably causes a serum AST increase (and ALT to a much lesser extent) that exceeds the serum ALT activity and can be further defined as muscle origin by the measurement of the serum creatine kinase activity (CK) a specific muscle enzyme. Clinical experience in veterinary medicine indicates that there is value in the interpretation of the serum activities of ALT and AST for liver disease. Following an acute injury resulting in a moderate to marked increase in the serum ALT and AST concentrations, the serum AST will return to normal more rapidly (hours to days) than the serum ALT (days) due to their difference in plasma half-life and cellular location. By determining these values every few days following an acute insult, a sequential "biochemical picture" indicative of resolution or persistent pathology is obtained.