Introduction

Almost every patient admitted to hospital will have their liver function tested, along with a full blood count, urea and electrolytes, glucose, and probably CRP.

A typical set of LFTS will include:

  • Bilirubincan show pre-hepatic, intra-hepatic and post-hepatic causes of jaundice. A patient won’t necessarily be visibly jaundiced if bilirubin is raised, especially if the bilirubin is not grossly elevated.
  • ALP – can be raised by liver, bone and placental pathologies. When raised in liver disease it indicates biliary obstruction and hepatic metastasis.
  • AST – is raised in liver and skeletal muscle pathologies
  • Albumin – low albumin indicates capilliary leak
  • GGT – is most useful to assess if raised ALP is due to liver, or other pathology.
  • INR – is also usually measured in suspected liver disease. This is essentially a measure of the liver’s synthetic function, as it measures the liver’s ability to produce clotting factors. In hepatitis and other liver pathologies, a raised INR indicates significant liver damage.

When LFT’s are routinely measured in patients coming up for surgery, an abnormality is found in 3.5% of people. 0.3% of patients have ALT levels 2x that of normal.
The majority of patients with abnormal test results have significant liver disease.
The two most common liver diseases are alcoholic liver disease, and non alcoholic fatty liver.
Normal LFT’s do not necessarily exclude the possibility of chronic liver disease.

ALT

Alanine transaminase – aminotransferase – 5-45 U/L
  • Can be raised up to 50x normal. When they are this high it suggests viral or drug induced hepatitis, or extensive hepatitis with necrosis of another source.
  • Normal levels in infants are 2x that of adults
  • This is an enzyme that catalyses a reaction between an amino acid and a keto-acid. Ultimately, they are important in producing various amino acids.
  • Found mainly in the liver, but also smaller amounts in the kidneys, cardiac and skeletal muscle. It, however, is fairly specific for liver damage.
  • During liver damage, ALT is released into serum causing raised levels that may remain high for weeks or months. Levels will be raised before jaundice appears.
  • Levels of ALT fluctuate slightly throughout the day, and are particularly raised after exercise.
  • It is generally raised in liver problems, and less so in problems with the bile duct. It may also be raised in heart problems.
  • More specific for liver damage than AST.
  • Levels of ALT and AST both raised above 2x normal then this is significant.
  • If the transferases are very high (greater than 1000 U/L then the diagnosis is almost certainly hepatitis
  • Alcoholic liver disease will never cause an AST of >1000 u/L

AST

Aspartate transaminase  – 5-45 U/L
  • Levels can go as high as 20x normal. This would normally indicate something like viral hepatitis, sever skeletal muscle trauma, extensive surgery, drug induced hepatic trauma,
  • Levels from 10-20x normal may suggest MI, and alcoholic cirrhosis.
  • 5-10x normal may suggest chronic cirrhosis
  • Mildly raised levels are often found it fatty liver (steatosis), liver metastasis and PE.
  • These type of enzymes have a similar function to ALT enzymes. These enzymes are found in the liver, RBC’s, cardiac and skeletal muscle, kidney and brain tissue. As a result, damage to any of these areas can result in an increased level on test result.
  • It used to be used as a marker for MI, but is not specific enough, and has been superseded by tests for troponins.
  • Remember, high levels are likely to be liver OR heart problems OR muscle damage (use other tests, namely ALT to help you decide)
  • Levels of AST tend to fluctuate depending on the amount of current acute damage. So levels will be highly raised with a lot of current necrosis, and may only be very slightly raised if there is no current necrosis (even though there may be very severe disease present). Therefore, AST can be used as a monitoring mechanism.

ALP

Alkaline phosphatase  – 25-110 U/L
  • These enzymes work best in an alkaline environment are involved in hydrolysis reactions – i.e. they remove a phosphate group from a molecule.
  • It is found in large concentrations in cells lining the bile duct and in bone. So when levels are raised in the plasma, it normally means damage to one of these areas. Levels can be physiologically elevated in times of high bone turnover, such as adolescence and in the third trimester of pregnancy.
  • ALP is likely to be largely elevated in bile duct blockage, and slightly raised in liver disease (e.g. hepatitis or liver cancer)
 

Gamma-GT 

GGT – <65 U/L
Raised levels are common in obstruction of the bile ducts. GGT is often used to confirm that AST readings are due to liver damage. GGT is used to particualrly monitor cirrhosis caused by alcoholism.
 

Bilirubin

1-20 µmol/l
Most commonly used to asses for obstructive jaundiceLevels also likely to be raised in liver damage and in cases of severe RBC damage. Test for urobilinogen can be useful in determining whether it is due to RBC’s or a problem with the liver / bile system.

Albumin

33-49g/l
This is the major protein constituent of plasma, and accounts for over 50% of all plasma proteins. It is manufactured in the liver from ingested amno-acids. It helps to regulate osmotic pressure as well as transport nutrients and waste products.
It may often be reduced as a result of;

  • Diarrhoea
  • Liver disease
  • Poor diet
  • Iron deficiency
  • Infection

Interpretations

  • ALP raised, ALT slightly raised – likely to be a problem in bile duct.
  • ALT raised, ALP slightly raised – likely to be a problem in liver.
  • Very high ALT, slightly raised AST – suggests viral / drug induced / severe necrosis of liver
  • AST raised, ALT slightly raised – suggests alcoholic or drug induced cirrhosis.

 

Patterns of L​FT results

There are two main patterns of liver function test results, and these help identify what the cause of the abnormal results are:

  1. Obstructive – due to bile duct obstruction. Remember this could be any part of the ducts, even the little tiny ones, within the liver itself, it doesn’t necessarily mean the common bile duct. This pattern will give:
    1. High bilirubin
    2. High ALP
    3. Normal ALT
  2. Hepatic – this is a sign of acute liver inflammation. The pattern will give:
    1. Very high ALT – between 200- 2000 U/L
    2. Varying bilirubin – the higher the level, the greater the degree of damage
    3. Slightly raised ALP – should be no higher than 2x normal.
    4. Increased prothrombin time – usually will be slightly raised. In cases of severe liver failure it may exceed 25seconds.
Test Result
Initial Action
Management Plan
↑ Bilirubin only
Check conjugated / unconjugated ratio to exclude haemolysis
Reassure – likely to be Gilbert’s Syndrome
↑ gamma-GT only
From history:
          Alcohol?
          Enzyme inducing drugs?
          Obese?

Reduce alcohol intake
No action
Lose weight

↑ ALP / ALT <2x normal
———————————————–
Reduce alcohol intake

Stop hepatotoxic drugs
Lose Weight (BMI>25)
Recheck LFT’s in 3-6 months

↑ ALP / ALT >2x normal (or <2x normal, but persistently high)
Further Tests:
          Hepatitis virus
          Autoimmune tests
          Ferritin
          USS liver
Dilated bile ducts:
          Cholangiography, ERCP
Normal bile ducts:
          Treat specific disorder

Adapted from a table in – Davidson’s Principles and Practice of Medicine. 20th ed. Churchill Livingstone, (2006), Boon, NA., Colledge, NR., Walker, BR.

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