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Liver disease investigation

ISSN 2398-2950

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Introduction

  • Accurate clinical evaluation of the liver can be accomplished by a series of diagnostic procedures.
  • Physical examination and a complete history of the patient are important in the diagnosis of liver failure, most signs are relatively non-specific.
  • The history is particularly important in differentiating acute from chronic disease.
  • Examination of urine and blood samples is therefore essential in the diagnostic process.
  • By far the most common liver disease in cats is cholangiohepatitis Liver: cholangitis which may be idiopathic or the result of bacterial infection.
  • In the USA, hepatic lipidosis Liver: lipidosis follows close behind on the differential list.
  • Tests can be divided into two categories, ie those indicating hepatocellular damage and those measuring hepatic function.
  • This approach is a guide to the investigation of liver disease and although examples of tests are quoted the lists are by no means complete.

Clinical presentation of liver disease

Signalment
Age Breed
  • Some breeds have congenital/familial renal disease, eg PSS in Persian cats.

Clinical signs

  • Clinical signs of liver disease are often non-specific and frequently overlap with signs associated with other conditions. Specific signs may raise a suspicion of liver disease which should be investigated, but remember that liver disease can be primary or secondary to other conditions.
  • Anorexia.
  • Depression.
  • Polyuria/polydipsia.
  • Weight loss.
  • Nausea, eg inappetence/anorexia, lip smacking, excessive salivation.
  • Vomiting or diarrhea.
  • Seizures (uremic encephalopathy in advanced liver failure).
  • Ascites.
  • Acholic feces.
  • Intolerance to sedation and anesthesia.
  • Gastrointestinal ulceration.
  • Hepatocutaneous syndrome.
  • Bleeding syndrome (acute onset collapse).

Clinical history

  • The clinical history may be important in determining the chronicity of any liver disease.
  • It is also vital to consider if there is any history of travel or exposure to drugs, toxins, supplements, etc.

Clinical examination

  • Palpation of liver size and shape:
    • Small liver may indicate cirrhosis or PSS.
    • Large liver may indicate acute inflammation, amyloidosis Amyloidosis, hypertrophy or infiltration, extramedullary aematopoiesis, passive congestion or neoplasia.
    • Hepatic pain is associated with acute inflammation.
  • Evidence of coagulopathy.
  • Evidence of ascites.

Diagnostic imaging

Diagnostic imaging studies provide anatomical information only and cannot be used to determine etiology of disease or functional information in most cases.
Radiography
  • Useful to determine size of liver Radiography: abdomen:
  • The shape of the liver may give a clue to the etiology of the disease:
    • Generalized enlargement indicated diffuse infiltrative disease.
    • Focal enlargement may be seen with lobar neoplasia or cysts.

Ultrasonography

  • Used to examine liver architecture  Liver: congestion - ultrasound (compare with normal Liver: normal - ultrasound). 
  • Coarse or nodular hyperechogenicity is common finding.
  • This is an essential modality in the presence of ascitic fluid.
  • Ultrasound can be used to guide biopsy and since the type of lesion cannot be differentiated by the use of ultrasound alone it is advisable to perform a biopsy if lesions are visible ultrasonographically.
  • May also be used to detect presence of portosystemic shunts.

Computed Tomography

  • Can be combined with angiographic studies for very sensitive evaluation of portosystemic shunting.
Hepatoportal angiography

Laboratory investigation

  • Where history and clinical signs are suggestive of liver disease, or in a particular breed with a predisposition to congenital liver disease, or a general health screen suggests liver involvement, further evaluation of liver function is necessary.
  • Try to answer the following questions:
    • Is there evidence of liver damage?
    • Is the damage affecting primarily the hepatocellular or biliary system?
    • Is there evidence of liver dysfunction?
    • What is the prognosis?
  • Laboratory screening tests are performed in any unwell animal. Indications for further investigation of the liver would include:
    • Elevations of concentrations of ALP, ALT, AST, bilirubin, GGT, cholesterol.
    • Reductions in blood urea, glucose, serum proteins.
    • Presence of bilirubin in urinalysis.
    • If ascites is present a sample should be collected for analysis.
Biochemical testing
Assessment of hepatocellular damage
  • Hepatocyte damage is assessed by measurement of enzymes released from damaged hepatocytes:
  • These enzymes are only released while damage is ongoing.
  • These enzymes are not liver function tests.
  • Animals with fibrotic livers may have severely impaired liver function but no active cellular destruction. Therefore, liver enzymes may be normal.
Alanine aminotransferase (ALT)
  • ALT is found within the cytoplasm of hepatocytes.
  • Considered most specific for diagnosis of liver damage.
  • Elevations in ALT crudely correlate with number of hepatocytes damaged although cannot show reversibility so the level is not prognostic.
  • Other important causes of elevation - hyperthyroidism Hyperthyroidism.
  • Much shorter half-life than in dogs (3-4 hours) therefore any elevation usually indicates ongoing disease.
Aspartate aminotransferase (AST)
  • AST is found in many cells.
  • Not specific for liver damage so elevated levels may be seen in other diseases.
  • If ALT is raised as well as AST, it is likely that the cause is liver damage.
  • Elevations in ALT crudely correlate with number of hepatocytes damaged.
  • If concentrations are markedly elevated suspect serious cellular injury.

Assessment of biliary damage

  • Cholestasis is the stagnation of bile flow and can be caused by intra- or extra-hepatic factors.
Alkaline phosphatase (ALP)
  • Serum ALP Blood biochemistry: alkaline phosphatase is a good indicator of cholestasis as it is readily released from bile duct before plasma bilirubin elevated.
  • It is released in relatively small amounts and has a relatively short half-life in cats (6 hours), thus small increases in ALP should always be thought of as significant.
  • Usually small rises in liver damage except in hepatic lipidosis when ALP concentrations increase dramatically.
  • Also increase in hyperthyroidism and core diseases may be increased in growing kittens.
Gamma glutamyltransferase (GGT)
  • GGT Blood biochemistry: gamma glutamyl transferase is found on surface of hepatocytes and bile duct epithelium.
  • GGT has a longer half-life than ALP.
  • More sensitive than ALP for detection of liver disease.
  • Elevations seen in hepatocellular damage and biliary disease.
Cholesterol
  • The liver is the site of cholesterol regulation.
  • Cholesterol Blood biochemistry: cholesterol concentrations may be reduced in severe hepatic failure and portosystemic shunts.
  • Biliary disease Bile duct: disease may result in increased cholesterol concentrations due to reflux from bile into blood and increased synthesis.

Hematology

Assessment of liver function

Cytological/Histopathological evaluation

  • A suspicion of liver damage will be raised by the clinical signs and history and diagnostic imaging may further support a diagnosis of liver involvement. However, confirmation of significant liver involvement can only be obtained using laboratory testing.
  • Samples of liver for cytology or histological analysis will help confirm significance of any imaging and clinical findings.
Fine needle aspirate
  • FNA Fine-needle aspirate can be used to collect a tissue sample for cytological examination Cytology: fine-needle aspirate.
  • This is most useful in cases of diffuse disease or in conjunction with ultrasound guidance where the chance of obtaining a representative sample is greater.
  • Rarely provides a definitive diagnosis.
  • Can be misleading especially with inflammatory disease and is generally regarded as only being useful in the diagnosis of infiltrative neoplastic disease (lymphoma) or lipidosis.
Liver biopsy
  • May provide information about pathogenesis of disease and etiology, except in cases of 'end stage' liver failure where the changes may be too advanced Biopsy: hepatic.
  • A number of methods of biopsy are described including tru-cut, surgical and laparoscopic.
Beware of tru-cut biopsies in cats as these have been associated with sudden death due to vagal shock therefore certain automated devices should be avoided.
  • Surgical biopsy is often chosen in cats due to the high rate of associated inflammatory pancreatic and gastrointestinal disease (triaditis), this therefore allows biopsy of multiple organs as indicated.

Is the liver involvement primary or secondary?

  • Many disease can cause secondary hepatic changes:
    • Inflammatory bowel disease/pancreatitis.
    • Hepatomegaly in diabetes mellitus.
    • Hepatic hypoxia due to poor perfusion in severe cardiac disease.
    • Hepatomegaly and damage due to right-sided heart failure and hepatic congestion.
These differentials have important implications for treatment and prognosis.
  • It is now increasingly recognized that many cats with inflammatory liver disease can have concurrent inflammatory pancreatic and gastrointestinal disease (triaditis). The link between these diseases is not fully understood but may involve translocation of bacteria. In cats, it is therefore vital to assess for evidence of these concurrent diseases as part of investigation into possible liver diseases.

Prognosis

  • Many authors have looked for prognostic indicators in liver disease however this if often difficult to determine
  • Poor prognostic factors include presence of ascites, presence of hepatic encephalopathy and alterations in acute phase proteins.
  • Cats with hepatobiliary disease are at risk of developing major complications, most notably coagulation disorders, they are also very good at hiding the severity of disease. Therefore, aggressive therapy is vital in this species in order to avoid a poor outcome.

Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.​
  • Gaschen L (2009) Update on Hepatobiliary Imaging. Veterinary Clinics of North America Small Animal Practice 39 (3), 439-467 PubMed.
  • Center S A (2007) Interpretation of liver enzymes. Veterinary Clinics of North America Small Animal Practice 37 (2), 297-333, vii PubMed.
  • Sherding R G (2000) Feline jaundice. J Feline Med and Surg (3), 165-169 PubMed.
  • Sutherland R J (1989) Biochemical evaluation of the hepatobiliary system in dogs and cats. Vet Clin North Am 19 (5), 899-927 PubMed.

Other sources of information

  • Rial S M (1995) Clinicopathologic evaluation of the liver. Vet Clin North Am 25, 257-273.

Further Reading