Diagnostics for hepatobiliary disease (Proceedings)
Clinical signs of gastrointestinal disease, such as vomiting and diarrhea are extremely common in small animal patients. When seeking advice from a veterinarian pet owners expect an accurate diagnosis and definitive therapy of the problem. In very few cases the diagnosis can be made by history and physical examination alone and the veterinarian has to utilize diagnostic tests to arrive at the diagnosis. The challenge for the veterinarian is to choose the most appropriate diagnostic test to arrive at the most accurate diagnosis.
In general, the clinician is guided by the golden rule to only perform a diagnostic test when the outcome of the test will have an impact on the management of the patient. This golden rule can be expressed more scientifically by stating that a diagnostic test should only be performed if the post-test probability for a disease is either significantly smaller or significantly larger than the pre-test probability. This means that the probability of a certain disease either needs to increase or decrease after the results of a diagnostic test have been received and interpreted.
While some diagnostic tests are either negative or positive, most diagnostic tests will yield a quantitative result that needs to be interpreted. This is achieved by comparison of the result found in a diseased animal to that found in a healthy animal (reference range, control range, or normal range). However, a result outside the reference range does not necessarily indicate disease and cut-off values need to be determined that afford the best test characteristics for the diagnosis of a disease. A result outside the reference range may have different implications for different tests. For example if the upper limit of the reference range for serum creatinine concentration is 133 µmol/L (1.5 mg/dL), a result of 150 µmol/L (1.7 mg/dL) may very well be significant, while a serum ALT activity of 76 U/L in a dog may be of no significance when the reference range is 0-65 U/L. Therefore, a cut-off value for each diagnostic test must be identified, that determines whether an abnormality is significant enough to warrant further clinical work-up or even a specific diagnosis of a disease.Imaging
Abdominal radiography has a limited usefulness for the diagnosis of hepatic disease in dogs and cats. Abdominal radiographs are most useful to evaluate hepatic size. Both hepatomegaly, for example due to hyperadrenocorticism or hepatic masses, and microhepatica, for example due portosystemic vascular anomalies or cirrhosis in dogs, can be appreciated on an abdominal radiograph, hepatomegaly should also be apparent on abdominal palpation. Also, calcifications of the hepatic parenchyma can be diagnosed by abdominal radiography.
In contrast to abdominal radiographs, abdominal ultrasound is very useful to evaluate the architecture of the hepatic parenchyma and the hepatic vasculature. Ultrasound can be used to evaluate the overall echogenicity of the liver and is helpful to compare the echogenicity to other abdominal organs. Abdominal ultrasound is also useful to identify isolated masses or lesions within the parenchyma. Abdominal ultrasound is also a great diagnostic tool to identify and localize portosystemic shunts. However, the success of the evaluation is greatly dependant on the expertise of the ultrasonographer and also on the patience in trying to identify the shunt vessel.
Transcolonic and transsplenic scintigraphy are very useful to definitively diagnose a portosystemic vascular anomaly and to determine the shunt fraction. However, they provide little information about the exact location of the shunt. A transsplenic approach is superior to a transcolonic approach as a smaller amount of radioactive tracer can be used and also there are less factors that might negatively influence the outcome of the examination.
Serum chemistry profile
Serum activities of hepatic enzymes are analyzed as markers for hepatobiliary disease in both dogs and cats. Unfortunately, some of these enzymes are also synthesized by other tissues. Therefore, increases of serum activities of hepatic enzymes outside the control range can be seen with many non-hepatic conditions.
Alanine amino transferase (ALT) is a cytosolic enzyme of hepatocytes and leaks into the vascular space during hepatocellular damage. The serum half-life for ALT is rather short (1-2 days). Mild increases of serum ALT activities are considered to be non-specific for hepatocellular injury but moderate to severe increases are cause for concern and should prompt immediate further work-up of the patient for possible hepatobiliary disease.
Alkaline phosphatase shows species-specific differences. In the dog, increased serum ALP activities are most commonly due to hyperadrenocorticism, iatrogenic drug therapy (glucocorticoids, phenobarbital, or other), or biliary disease. However, primary hepatic disease can also be associated with increases of serum ALP activities. In cats, serum ALP activities are more specific for hepatobiliary disease.
Gamma glutamyl transferase is also non-specific for liver disease in dogs and cats but is more sensitive for liver disease in cats than it is in dogs.
Serum blood urea nitrogen, cholesterol, albumin, and glucose concentrations can all be decreased in dogs and cats with hepatic failure. However, these findings are rather insensitive and are also not specific for hepatic failure. Also, the liver synthesizes several coagulation factors and hepatic failure can thus lead to coagulopathies and abnormalities on a coagulation profile. It should be noted that the synthesis of these various molecules does not require the same degree of hepatic function. Serum albumin and cholesterol concentrations can be abnormal early during hepatic failure, while coagulopathies and hypoglycemia only occur in end-stage hepatic failure.