Faculty of Veterinary Medicine, Clinic of Small Animal Medicine, Centre for Clinical Veterinary Medicine, LMU Munich, Munich, Germany
Liver Diseases - Indications for Invasive Sampling in Dogs
In order to diagnose a subacute or chronic liver disease, it is often necessary to obtain samples for cytological or histological examination by performing liver biopsy. Before a biopsy is performed, extrahepatic causes of elevated bilirubin and serum enzyme activities, portosystemic vascular anomaly, and acute events such as drug reactions, intoxication or leptospiral infection should be excluded. In addition, coagulation parameters should be measured, and anesthesia suitability should be assessed individually for each patient.
Indications for liver biopsy are the following:
1. Chronically elevated serum enzyme activities
(alanine aminotransferase [ALT], aspartate aminotransferase [AST])
2. Abnormal liver function tests
3. Structural liver changes
4. Specific breed-associated liver diseases
1. Chronically Elevated Serum Enzyme Activities
Since liver diseases cause unspecific clinical symptoms (e.g., vomiting, diarrhea, polyuria), one often thinks of hepatopathy when serum enzyme activities are elevated. However, before focusing on the liver, extrahepatic causes of increased enzyme activities need to be ruled out (e.g., cortisone administration, endocrinopathy, pancreatitis). If enzyme activities, which can be indicators of hepatic cell damage (ALT, AST), are elevated three times in succession within two weeks in a young to middle-aged dog, this indicates a chronic and potentially progressive hepatopathy (e.g., chronic hepatitis, copper accumulation). In that case, liver biopsy should also be performed in an asymptomatic patient to diagnose or exclude a clinically relevant liver disease. If a chronic progressive liver disease remains unrecognized, it will lead to irreversible liver damage (liver fibrosis).
2. Abnormal Liver Function Tests
In a serum profile, concentrations of some parameters (albumin, urea nitrogen, bilirubin, cholesterol, glucose) reflect the liver function. However, destruction of the liver tissue must be significant (>70–80%) before concentrations of these parameters are altered. Concentrations of serum bile acids are more sensitive in detecting a functional disorder of the liver. In cases with increased concentration of serum bile acids, an invasive diagnostic method is often necessary to clarify the cause. Before a liver biopsy is performed, portosystemic vascular anomaly and posthepatic cholestasis should be excluded.
3. Structural Liver Changes
During the ultrasonographic examination of the liver, focal structural changes of the liver are frequently seen in older dogs. Conventional ultrasonographic examination usually cannot distinguish between benign (e.g., hyperplastic liver nodules, hematoma) and malignant (e.g., primary tumor, metastasis) alterations. A tissue sample is necessary for the exact assessment of the altered liver areas. Additionally, a contrast ultrasonographic examination of the liver can be performed, with a diagnostic accuracy of 96% for the malignant structural changes. This less invasive examination method is a valuable alternative to a liver biopsy and is offered by some referral veterinary centers. It is especially useful in older animals, in which benign structural changes occur frequently, since it avoids the risk of bleeding and of anesthesia.
4. Specific Breed-Associated Liver Diseases
Some dog breeds are predisposed to hepatobiliary diseases. In cases of suspected congenital portosystemic vascular anomalies (stunted growth in young animals, chronic symptoms, typical breed such as Cairn Terrier, Yorkshire Terrier, Shih Tzu, Irish Wolfhound, Maltese), concentration of serum bile acids should be measured. In cases of elevated concentration of bile acids, imaging of the abnormal blood vessels should be performed, and a liver biopsy is not indicated. In breeds which are predisposed to idiopathic inflammation (e.g., Cocker Spaniels, English Springer Spaniels, Standard Poodles) or increased copper storage (e.g., Labrador Retrievers, Dobermans, Bedlington Terriers, West Highland White Terriers), liver biopsy should be taken at a time when no clinical symptoms or signs of hepatic dysfunction are present. A mild elevation of ALT is often the only indication of chronic progressive liver disease. In addition to a conventional staining with hematoxylin and eosin (H&E), a histological copper staining (rhodanine staining) should be carried out in each dog to identify a primary or secondary copper storage disease.