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33 MAY/JUNE 2017 ■ TVPJOURNAL.COM CONTINUING EDUCATION shorter half-life, increases of serum ALP activity are more specific for hepatobiliary disease than in dogs and are generally clinically relevant. Gamma-Glutamyltransferase GGT is associated with the cell membranes of hepatocytes that form the bile canaliculi and bile ducts, as well as periportal hepatocytes. It is a marker of intrahepatic (eg, feline hepatic lipidosis) or extrahepatic (eg, bile duct obstruction) cholestasis. In dogs, it has a higher specificity (87%) and lower sensitivity (50%) for hepatobiliary disease compared with ALP. 7 In general, GGT is a more sensitive marker of feline hepatobiliary disease than ALP. However, in cats with feline hepatic lipidosis, GGT is generally only mildly elevated. 8 No definitive studies determining the half-life of GGT have been performed in cats or dogs. However, serum GGT and ALP activities decrease after liver injury at a similar rate in dogs, suggesting that they have a similar half-life. 9 Interpreting Liver Enzyme Elevations The degree of the increase in hepatocellular-damage enzyme activities may help stratify disease severity as follows 5 : • Mild: 2- to 3-fold elevation in activity • Moderate: 5- to 10-fold elevation in activity • Marked: >10-fold elevation However, such increases do not always correlate with severity of disease. This is true in dogs and cats with portosystemic shunting and dogs with end-stage chronic hepatitis, in which hepatocytes are replaced by fibrous tissue. Therefore, the degree of liver enzyme increase should be interpreted with caution. Because the liver has a large regenerative capacity, the degree of liver enzyme elevation should also not be used to indicate prognosis. For example, a dog with acute liver injury may have severely increased serum ALT activity but can still make a full recovery. Longitudinal monitoring trends in liver enzyme activities can help in determining chronicity and monitoring disease progression and/or response to treatment. In evaluating liver enzymes, it is important to determine what type of elevation pattern is present (ie, hepatocellular damage versus cholestasis). A relatively greater increase in ALT and AST activity indicates hepatocellular damage, while a greater increase in ALP and GGT activity indicates cholestasis, which could be intrahepatic or extrahepatic. Establishing the pattern may help narrow the differential diagnosis. However, some liver diseases can display a mixed pattern (eg, cholangitis, phenobarbital hepatopathy). LIVER FUNCTION TESTING Routine biochemical testing can give clinicians an insight into many liver functions. Box 2 presents common abnormal results of biochemical tests that can have liver-related causes as well as important differential diagnoses to consider for these test results. However, because of the liver's functional reserve capacity, these tests are not sensitive for liver insufficiency. Abnormal results can also be caused by other conditions and thus also lack specificity. It is important for clinicians to not only look for analytes that are flagged as being outside their respective reference intervals but also look at their actual values. For example, serum albumin, cholesterol, and blood urea nitrogen (BUN) concentrations toward the lower limit of the reference interval suggest hepatic insufficiency or portosystemic shunting. Monitoring trends in these values over time can also be informative. Because of the limited sensitivity and specificity of biochemical tests, patients with confirmed or suspected liver disease sometimes require additional liver function testing to better characterize their disease. Serum Bile Acids Measurement of the total concentrations of serum bile acids (SBA) aids in the diagnosis of patients with portosystemic shunts and in the assessment of hepatic function. Potential indications for SBA measurement include: • Suspicion for portosystemic shunting (eg, seizures, other signs of encephalopathy) • Persistently increased liver enzyme activities, especially ALT