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Liver Function Tests

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Overview

The term ‘liver function tests (LFTs)’ is a misnomer, as they mainly test the level of damage that has occurred to the liver, rather than its function. They are often also called liver blood tests. A summary of key liver function test patterns is discussed below.

LFTs often include:

Other tests that may be considered are:

Liver Function Test Patterns

Overview

Liver function tests can have different patterns according to the site affected. They may be described as hepatocellular or cholestatic patterns. It is important to note that these patterns can overlap as many of their causes can cause damage to surrounding tissues.

For example, cholangiocarcinoma may initially present with post-hepatic jaundice with cholestatic liver function tests, but if the tumour invades the liver, pre-hepatic jaundice and hepatitic liver function tests can arise.

Isolated rise in bilirubin

An isolated rise in bilirubin can be assessed using conjugated and unconjugated bilirubin:

  • Elevated unconjugated bilirubin:
    • Suggests a pre-hepatic cause as the liver has not yet conjugated bilirubin (e.g. haemolysis or Gilbert’s syndrome)
    • It may suggest severe liver disease if the liver cells can no longer conjugate bilirubin
  • Elevated conjugated bilirubin:
    • Suggests an intra-hepatic cause as the liver cells can conjugate bilirubin, but it ‘leaks out’ into the blood due to:

Initially in liver disease, a mixture of elevated conjugated and unconjugated bilirubin is seen. In later stages, the liver cells cannot conjugate bilirubin, and only elevated unconjugated bilirubin may be seen.

Hepatocellular pattern

A hepatocellular pattern is seen when liver function tests show elevated alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) out of proportion to ALP and GGT.

This is because AST and ALT are made more in the liver than the biliary tree and suggest hepatic disorders affecting the liver itself (e.g. hepatitis).

Other key points include:

  • ALT often rises more than AST in acute liver damage
  • AST/ALT >1000 IU/L are strongly suggestive of hepatitis (e.g. drug-induced, viral, autoimmune etc.)
  • The ratio of AST:ALT can help with identifying the cause:
    • Chronic liver disease: ALT > AST
      • Once cirrhosis occurs: AST > ALT
    • AST:ALT ratio >2 suggests alcoholic liver disease
      • This can be remembered with ‘I propose a toAST’
    • AST:ALT ratio <1 suggests non-alcoholic liver disease

If the disease process involves the biliary tree, ALP and GGT may rise, resulting in overlapping results.

Cholestatic pattern

A cholestatic pattern is seen when liver function tests show elevated alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT) out of proportion to aminotransferases (ALT and AST).

This is because ALP and GGT are made more in the biliary tree than the liver and suggest post-hepatic (obstructive) disorders (e.g. bile duct obstruction, pancreatic cancer etc).

If the disease process involves the liver, AST and ALT may rise, resulting in overlapping test results.

Bilirubin

Overview

Bilirubin is the resulting product of haem breakdown:

  • Total bilirubin measures both conjugated (direct) and unconjugated indirect) bilirubin
  • Conjugated and unconjugated bilirubin can help to identify where the problem is if there is hyperbilirubinaemia. See Jaundice for more.

Unconjugated bilirubin is bilirubin that has not yet been metabolised by the liver cells. Once metabolised, it becomes conjugated bilirubin.

Transaminases (ALT and AST)

Overview

An umbrella term for the enzymes alanine transaminase (ALT) and aspartate transaminase (AST) which are produced in the liver, kidneys, muscle, and heart.

Elevated transaminases may suggest liver disease as they ‘leak out‘ of damaged liver cells

Alanine transaminase (ALT)

Alanine transaminase (ALT) is mostly found in the liver but is also present in the kidneys, muscles, and heart. ALT is found in the cytoplasm of cells, meaning increased levels can suggest cell damage and leakage.

Aspartate transaminase (AST)

Aspartate transaminase (AST) is less specific than ALT for the liver, as it is mostly found in the mitochondria of cells, and more is present in the kidneys, muscles, and the heart, alongside the liver. Raised AST levels suggest liver, heart, kidney, or muscle damage.

Gamma-glutamyltransferase (GGT)

Overview

Gamma-glutamyltransferase (GGT) is found in hepatocytes, biliary epithelial cells, the kidneys, and intestines.

Elevated GGT may suggest liver or biliary disease. It is best used in combination with alkaline phosphatase (ALP):

  • All liver diseases may show increased GGT levels
  • Like ALP, increased GGT levels suggest cholestasis
  • GGT can confirm that a raised ALP is due to liver damage and not another cause

Alkaline Phosphatase (ALP)

Overview

Alkaline phosphatase (ALP) is an enzyme found in cells lining the bile ducts but also in bone. It is involved in the calcification of bones. Elevations may suggest biliary or bone disease. It is best used in combination with gamma-glutamyltransferase (GGT):

  • An elevated ALP (often with elevated GGT) suggests cholestasis
  • A high ALP with normal GGT suggests bone disease

It is important to note that ALP is physiologically increased in pregnancy, and can be as high as 3 times the upper limit of normal.

Albumin

Overview

Albumin is a sensitive marker of liver function, as it is mostly made in the liver. Since it has a long half-life, it is not as useful in acute disease. Reduced levels of albumin can cause oedema.

It is not specific, as decreased albumin can occur due to causes other than liver dysfunction. Some causes can include:

  • Impaired synthesis: chronic liver disease (e.g. cirrhosis)
  • Loss of albumin: such as in nephrotic syndrome, as it is lost through the urine

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