Introduction

The clinician should always give careful consideration to the reasons behind taking a biopsy: you take a biopsy to give you a diagnosis, prognosis and/or guidelines for treatment. There is no clinical justification for undertaking a procedure as invasive as a liver biopsy unless it changes treatment decisions – doing it for ‘interest’ is certainly not justified. However, because the results of blood and imaging tests are non-specific in liver disease, some form of liver biopsy is usually indicated to give a diagnosis and allow most effective treatment. The clinician must then decide the best way to perform this biopsy considering how stable the patient is, the financial resources of the owner and the relative reliability of the results obtained with different methods.

Biopsy Methods

There is also little point in taking a biopsy which is not representative of the underlying disease – if the sample is too small, or from the wrong place, or only from one of a number of organs affected with disease, it may lead to the wrong conclusions being drawn and the wrong, or incomplete, treatment protocols.

Not all biopsies are created equal. The options for liver biopsy are:

• Fine needle aspiration (FNA) cytology – not strictly a biopsy but worth considering here as a potential alternative to more invasive biopsies
• Ultrasound-guided TruCut biopsy
• Wedge biopsy – at laparotomy or laparoscopy

Before undertaking any biopsy, except FNA, the clinician must check coagulation times and platelet count. This is even more important in cats than dogs because cats with liver disease have a higher prevalence of coagulopathies than dogs. This may be because of the high prevalence of biliary tract disease in cats resulting in fat malabsorption and vitamin K deficiency. This problem is compounded if they have concurrent inflammatory bowel disease and/or chronic pancreatitis causing exocrine insufficiency. At least a whole blood clotting time and platelet count on the feathered edge of a blood smear should be performed prior to canine and feline liver biopsies, and there is a rational argument for parenteral vitamin K treatment for 12–24 hours prior to biopsy in all cats.

Fine Needle Aspiration (FNA)

Beware becoming ‘liver FNA happy’ for fear of false diagnoses and wasting the client’s money! FNA of the gall bladder has a primary indication in the diagnosis of ascending biliary tract infections in dogs and cats – in fact, it is the best (perhaps only effective) way of doing this and is much more sensitive than liver culture or histopathology of a liver biopsy. It allows bile cytology and culture and selection of an appropriate antibiotic based on the results of culture and sensitivity. So, if ascending cholangitis is a differential, a careful bile aspirate should be performed. However, FNAs for anything else can be misleading: this is because of the ‘selective’ nature of aspirates – only things which will aspirate up a needle will be harvested and there is no anatomical information, so this is a very poor way of diagnosing diffuse liver disease such as chronic hepatitis, which is the commonest liver disease in dogs. There is a moderate indication in suspected hepatic lymphoma and feline hepatic lipidosis, but even those cases can be misleading. Willard et al. (1999) reported four cats in which fine-needle aspirate cytology suggesting hepatic lipidosis was misleading – in three cases, there was cholangiohepatitis on histology and in one case there was lymphoma. This is not to say that FNA does not have an important place in the diagnosis of feline hepatic lipidosis – cats in the acute phase of the disease on presentation are rarely well enough to have a general anaesthetic and more invasive biopsies. A rapid diagnosis with FNA allows initiation of supportive therapy and tube feeding. However, if the cat fails to respond appropriately after several days of feeding, consideration should be given to obtaining a liver biopsy.

Ultrasound-guided TruCut biopsies

These are less invasive than a laparotomy but do carry some risk – particularly of haemorrhage, so the dog or cat needs monitoring closely for about 12 hours after the procedure. Particular care should be taken in cats and the semi-automatic biopsy guns should be avoided in this species as they can cause significant mortality. Ultrasound-guided biopsies can be less representative than wedge biopsies – probably because of the small size of the sample. This problem is more serious in dogs than in cats with chronic liver disease. Cole et al. (2002) compared the diagnosis made on ultrasound-guided needle biopsies with wedge biopsies of the liver in 98 dogs and 26 cats and found the morphological diagnoses agreed only 48% of times.

Wedge Biopsies at Laparotomy or Laparoscopy

Wedge biopsies at laparotomy or laparoscopy. These have the advantages of being more reliable diagnostically and also of allowing concurrent pancreas and intestinal biopsies to be taken to rule in or out concurrent pancreatitis and/or inflammatory bowel disease. A feeding tube can be placed and the patency of the bile duct checked – all very useful. However, there is also a significant morbidity associated with these procedures – particularly with the concurrent gut biopsies – and a small but important risk that the cat may die as a result of complications of surgery. The risk-benefit balance therefore has to be carefully discussed with the owner before the method of biopsy is decided upon.

Interpreting the Liver Biopsy Histology Report

On the liver biopsy, the clinician should not just read the bottom line diagnosis but should read the whole report. It is important first in dogs to be sure this is a primary hepatitis and not a reactive hepatopathy. Sometimes the final diagnosis isn’t clear; for example if the pathologist has written ‘reactive hepatitis’ without a full explanation, the clinician may believe this is primary liver disease when in fact it is secondary. The presence of inflammatory cells alone does not mean primary disease – if there is no fibrosis and no evidence of hepatocyte death, this is not a primary hepatitis.

In primary hepatitis cases in dogs, the clinician should assess the amount and distribution of inflammation and the types of inflammatory cells involved, the degree and distribution of fibrosis and the presence of any obvious cause including buildup of copper. Combining all this information allows optimal treatment of the patient. It is not possible – and indeed is potentially dangerous – to give specific treatments for CH (such as copper chelators and steroid or other immunosuppressive therapy) without biopsy confirmation of disease. It is very important that all canine hepatitis cases have a copper stain performed and if the laboratory has not already done this, it should be requested.

If a significant amount of copper is found in the biopsy, in proportion to the severity of the disease, copper storage disease should be strongly suspected and treated with chelation and dietary therapy. If copper storage disease is ruled out, the type and distribution of inflammation present may suggest a cause for the disease. If there is a strong neutrophilic component, particularly if it is periportal, there may be a chronic hepatic or biliary tract infection and consideration should be given to culturing bile or liver and ruling out chronic partial extrahepatic biliary obstruction or cholecystitis.

Ideally, a bile sample should be taken for culture every time a liver biopsy is taken, as a routine procedure: it is very annoying to get back the biopsy result and then wish you had taken a bile culture at the time! If there is a granulomatous inflammatory response, it might be worth considering PCR for Bartonella or other unusual infections or submitting a sample to Cornell or Bristol UK for fluorescent in situ hybridisation (FISH) for bacteria. If there is a dense lymphoplasmacytic inflammatory component, an autoimmune aetiology might be considered. However, it is important to note that lymphoplasmacytic infiltration might also be seen in viral disease and at the current state of knowledge it is impossible to be differentiate between putative viral and autoimmune hepatitis in dogs, so the most difficult decision to make may be over the use of steroids.

References

1.  Willard MD, Weeks BR, Johnson M. Fine-needle aspirate cytology suggesting hepatic lipidosis in four cats with infiltrative hepatic disease. J Feline Med Surg. 1999;1(4):215–20.

2.  Cole TL, Center SA, Flood SN, Rowland PH, Valentine BA, Warner KL, Erb HN. Diagnostic comparison of needle and wedge biopsy specimens of the liver in dogs and cats. J Am Vet Med Assoc. 2002;220:1483–90.