Liver function assessment
- Assessment of the functional capacity of the liver is a useful component to the investigation of liver disease, allowing us to be aware of potentially dangerous complications and to give some idea of severity of any disease encountered.
- There is no single test which allows us to comprehensively assess liver function, rather it is a case of using a combination of tests to build an overall picture.
- Assessment typically involves blood analysis.
- This approach is a guide to the assessment of liver function.
- Whilst clinical examination is often only a small part of liver function assessment there are some indicators that may increase our clinical suspicion of disease:
- Icterus .
- Evidence of inappropriate bleeding suggestive of coagulopathy (petechiae , hematuria Hematuria, etc).
- Presence of ascites .
- Physical examination and a complete history of the patient are important in the diagnosis of liver failure, most signs are relatively non-specific.
Routine blood sample analysis
- The liver is important for synthesis of albumin Blood biochemistry: albumin and globulins Blood biochemistry: total globulin.
- In severe hepatic disease synthesis of these is reduced and hypoproteinemia Hypoproteinemia as a result of hypoalbuminemia or occasionally hypoglobulinemia (or both) may result.
Be aware that, in some cases of severe liver disease hypergammaglobulinemia is present which can normalize the total protein level.
- Albumin has a half-life of 8-10 days in cats and dogs and at least 80% of functioning hepatocytes must be lost before hypoalbuminemia occurs making this a marker of severe chronic hepatic disease.
- This hypoproteinemia may cause ascites or contribute to ascites in cases with portal hypertension.
- Urea is synthesized in the liver as a method of detoxifying ammonia absorbed from the gut.
- In severe liver disease urea concentrations may be reduced Blood biochemistry: urea.
- Do not rely on low urea levels to indicate liver dysfunction - it is not specific.
- Glycogen is synthesized in the liver as a storage mechanism for glucose and, in prolonged starvation, the liver is the main site of gluconeogenesis.
- In severe liver failure hypoglycemia may develop Hypoglycemia.
- Hyperbilirubinemia can be pre-hepatic (due to hemolysis), hepatic or post-hepatic (due to bile duct obstruction) Blood biochemistry: total bilirubin.
- Remember in hemolysis the liver's ability to conjugate bilirubin may be overwhelmed and icterus can develop without liver dysfunction.
- Bilirubinuria is always abnormal in cats.
- Hyperbilirubinemia, when pre and post-hepatic causes have been excluded, suggests liver dysfunction.
- Do not use the ratio of conjugated to unconjugated bilirubin to differentiate liver disease from cholestasis, it is rarely beneficial.
- Be aware that if total bilirubin is increased there is no benefit in running dynamic bile acid testing as cholestasis and the bilirubin itself will interfere with the test.
Dynamic liver function testing
Bile acid stimulation test
- Bile acids are synthesized in the liver and released through the bile ducts to the intestine and then taken up in the portal circulation and recycled.
- They should not appear in the circulation in significant concentrations.
- The stimulation test is performed by measuring peripheral blood concentration pre- and post-prandially (2 hours after feeding) - rising bile acids is a more sensitive indication of abnormal hepatic function.
- Normal bile acid metabolism requires normal hepatic vasculature, normal hepatocytes and a normal biliary tract therefore abnormal levels are not specific for intrinsic liver disease.
- The specificity of serum bile acids improves as the cut-off level increases, with levels between 20 and 40 mmol/L considered a grey area Blood biochemistry: bile acid.
- A serum bile acid level of above 100 mmol/L has high specificity for hepatobiliary dysfunction.
- This is the test of choice for portosystemic shunting Congenital portosystemic shunt (CPSS) which is usually accompanied by bile acid levels above 100 mmol/L
Other tests of liver functionClotting parameters
- The liver has an important role in the synthesis of particular clotting factors.
- Spontaneous bleeding is rare in animals with liver disease.
- Clotting parameters should always be checked prior to biopsy.
- Both indicative of severe hepatic dysfunction.
- Platelet dysfunction may also occur in liver disease Hematology: platelet count.
- Ammonia absorbed from the gut is detoxified in the liver.
- Increasing ammonia Blood biochemistry: ammonia concentrations in peripheral circulation can result in signs of hepatic encephalopathy Hepatic encephalopathy.
- Ammonia is difficult to measure accurately in blood as it is volatile and analysis must be done soon after sampling.
- Testing of dynamic bile acids is therefore usually preferred when assessing for hepatic encephalopathy.
- If ascitic fluid is present a sample should be collected for analysis.
- True transudate associated with failure to produce albumin.
- Modified transudate associated with portal hypertension.
- Protein C is an anticoagulant protein produced by the liver.
- Low protein C activity has been documented in dogs with hepatobiliary disorders, in particular portosystemic shunts.
- The utility of this protein in cats is still under investigation.
- Protein C is difficult to measure as it must be run within 24-48 hours of sampling and shipped on ice.
- Although imaging can give information about hepatic structure no imaging tests indicate liver function.