Liver function tests

Summary

  • ALWAYS INTERPRET WITHIN THE CLINICAL CONTEXT i.e. why were LFTs done in the first place; what is the trend; what is the most likely explanation and are more investigations required?
    • With regard to the latter, consider liver USS; other bloods e.g. FBC, ferritin (haemachromatosis), viral / autoimmune screens, A1AT, AFP, copper/caeruloplasmin; lifestyle advice, etc

Normal Reference Ranges (NB different hospitals may have different reference ranges)

  • Bilirubin (<21μmol/l)
  • Alanine transaminase – ALT (<40 IU/l) (NB AST levels have a similar reference range)
  • Alkaline phosphatase – ALP (35-104 IU/l if under 60yo; 40-129 IU/l if >60yo)
  • Total Protein (60-80 g/l)
  • Albumin (35-50 g/l)
  • Gamma glutamyl transferase – GGT (7-33 IU/l for women and 11-51 IU/l in men)

Bilirubin

  • Bilirubin is a byproduct of the breakdown of the haem molecule during the breakdown of RBCs (in the reticuloendothelial system e.g. spleen)
    • Unconjugated bilirubin is then taken to the liver for conjugation (making it water soluble so to be excreted via the urine)
  • A rise in bilirubin ONLY is relatively uncommon- most cases due to Gilbert’s syndrome
    • Other causes include increased haemolysis (check FBC; films; LDH); drugs
    • It may be useful to measure unconjugated and conjugated levels as conjugated bilirubin is normally a sign of liver/biliary disease (commonly obstructive)
      • Rarely Dubin-johnson sydrome

Albumin

  • The main serum protein, albumin is produced by the liver (marker of liver function)
    • Note that albumin has a long half life (20 days) so can not be used as a marker of acute liver function
    • Note also that albumin levels correlate negatively with systemic inflammation (i.e. negative inflammatory marker)
  • Albumin levels are unlikely to be a marker of significant liver disease without any other abnormal LFTs- however they can be used as a prognostic factor in chronic liver disease

Total Protein

  • Measures albumin and globulins.  Globulin production tends to rise disproportionately as albumin levels fall so this will often be high in liver disease and chronic inflammatory conditions.

Transferases (ALT/AST)

  • ALT is found in the cytoplasm of cells and AST in the mitochondria (ALT is more specific for hepatocytes; AST can also be found in skeletal muscle, cardiac muscle and RBCs) transferases are most commonly used as a measure of cell death/damage (usually due to inflammation)
    • Occasionally the ratio of AST:ALT can be useful in chronic liver disease
      • <1 (i.e. more ALT) suggests chronic liver disease/non-alcoholic; >1 suggests cirrhosis; >2 suggests alcoholic disease
  • A rise in ALT/AST > ALP/GGT suggest hepatocellular disease e.g. alcoholic hepatitis/cirrhosis; drug induced hepatitis (including paracetamol- often with a marked rise in ALT); Viral hepatitis (also marked ALT rise); autoimmune disease (mild increases in non hepatitic disease e.g. IBD); fatty liver disease (mild increase)
  • Untitled picture

ALP

  • Found mainly in cells lining the bile ducts (i.e. extrahepatic marker) but is also found in bone
  • Marked elevation usually a marker of cholestasis (with raised GGT) or increased bone metabolism (without)
  • A rise greater (but still associated with a rise in) than ALT suggests an extrahepatic problem – usually obstruction e.g. gall stones; can be seen also in primary biliary cirrhosis and primary sclerosing cholangitis
    • NB an isolated rise in ALP is the most common blood abnormality seen in medicine (can be seen in IBD, diabetes, hyperthyroidism, infections …)! However, it is still important to take into clinical context- consider increased bone metabolism (e.g. primary hyperparathyroidism, bone metastases)

GGT

  • Not routinely measured: Marker of extrahepatic damage (bile ducts) although is quite sensitive for alcohol induced damage.
    • NB may also be raised in viral hepatitis

For a relatively good guideline document on abnormal LFTs see here

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