Read the German translation: Diagnostisches Vorgehen bei Erkrankungen von Leber und Gallengängen

Feline and canine diseases of the liver and biliary system are species-specific. Therefore the diagnostic approach recommended to practicing veterinarians dealing with clinical problems differs between both species. In cats almost all primary disorders originate in pathologies of the biliary system. Therefore abdominal ultrasonography and fine needle aspirates of the liver, as well as collection of bile samples are indicated at an early time point during clinical workup.

Elevated Liver Enzymes in Asymptomatic Patients

In a study of more than 1000 blood samples from clinically healthy dogs and cats 39% of the samples showed elevated alkaline phosphatase (ALP), and 17% elevated alanine amino transferase (ALT).¹ Abnormal biochemical blood results for evaluation of the hepatobiliary system can result from 3 underlying pathologies: 1) hepatocellular damage (often in dogs), 2) Cholestasis (dogs and cats), 3) decreased liver metabolism (dogs).

Unfortunately blood tests are generally not specific enough to allow for the differentiation between primary or secondary liver problems. Moreover, these tests do not allow distinction between the different etiologies of a primary liver problem. Furthermore, the magnitude of liver enzyme elevation is not a reliable indicator of the prognosis or reversibility of a liver disease. Therefore procurement of liver biopsies (in dogs) or fine-needle aspirates (in cats) is always indicated.

My Approach

If no explanation for the liver enzyme abnormalities can be found and the patient is asymptomatic, the author recommends rechecking the laboratory abnormalities after 4-6 weeks (with the exception of Doberman Pinschers, that require immediate investigation with a liver biopsy). Measurement of serum bile acids may be useful if the decision to wait for a month seems too conservative.

Abnormal bile acids indicate hepatic or circulatory abnormalities, and such a patient should undergo further evaluation. If the bile acids are normal in an asymptomatic patient, the animal can wait a month before further workup is initiated if the liver enzymes are still increased.

Repeatedly abnormal liver enzymes should not be ignored, but should prompt a systematic investigation including liver function testing, ultrasonography and sampling of liver biopsies.

Liver Function Tests

Liver function tests include measurement of bilirubin, albumin, glucose, BUN, and cholesterol.^2-5

Albumin is exclusively made in the liver and a low concentration can indicate hepatic dysfunction (greater than 60% hepatic dysfunction, differential diagnoses for low albumin are renal, GI, or dermatologic loss, sequestration and dilution).

Clotting factors are made in the liver (except factor 8) therefore prolonged clotting time suggests hepatic dysfunction.

The fasting serum total bile acid concentration is a reflection of the efficiency and integrity of the enterohepatic circulation but non-specific for a particular type of liver dysfunction.⁵ Occasionally higher fasted BA values occur compared to postprandial BA values. Possible explanations could be individual variations in the release of bile acids (individual peaks by chance just before sampling), and a suboptimal stimulation from feeding.

In Utrecht ammonia is measured for evaluation of liver function. Samples must be put on ice directly or immediately measured (feline plasma samples are less sensitive). Erythrocytes contain two to three times as much ammonia as plasma, therefore hemolysis will increase blood ammonia. Failure of the liver to detoxify ammonia or shunting of portal blood away from the liver results in hyperammonemia. Liver dysfunction must be severe for blood ammonia concentrations to rise, but ammonia is very sensitive in the detection of shunting.

In the ammonia tolerance test (ATT), a baseline blood ammonia value is determined after a 12-hour fast. The animal is then given an exogenous load of ammonium per rectum and blood ammonia determined 20 and 40 minutes post challenge. For the rectal ATT, 2mL/kg of 5% NH4Cl2 is inserted into the rectum with a soft catheter. Blood ammonia should not increase any more than twofold (maximum 60 mg/kg, in Irish Wolfhound 120 mg/kg).

Ultrasonography and Fine Needle Biopsy

Ultrasonography is useful for identifying focal liver lesions, diffuse liver disease or biliary disease. Although fine needle aspiration (FNA) is safe and easy to perform, misinterpretation of results is possible and significant disease may be missed, particularly in cases with chronic hepatitis, cirrhosis, or lymphocytic cholangitis. The best correlation between FNA and liver biopsy can be found with infectious diseases, hepatic neoplasia and diffuse vacuolar hepatopathies.

Liver Biopsy

After examination of a coagulation profile reveals normal fibrinogen, liver biopsy may be performed during exploratory surgery (skin punch device, do NOT sample from the edge of a lobe), during laparoscopy or using an adequate biopsy needle. Sufficient clinical and laboratory data on the patient should be provided to the pathologist with the biopsy samples. Moreover, personal discussion of results generally improves the accuracy of histology.

Figure 1. Diagram for diagnostic work-up of a dog with increased serum liver enzymes.

References

1.  Comazzi S. Journal Small Animal Practice (2004) 45. 343-349,

2.  Webster CRL. In: Ettinger SJ, et al. (editors). Textbook of Veterinary Internal Medicine. St. Louis: Elsevier Saunders (2005),

3.  Center SA, et al. JAVMA (1992); 201(8):1258,

4.  Bunch S. In: Nelson RW, et al. Small Animal Internal Medicine. St. Louis: Mosby (2003),

5.  Trainor, et al. J Vet Int Med 17: 145-153 (2003).