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Appendix 1 - Pathophysiology of liver function tests
ALT – (alanine aminotransferase) an enzyme involved in the recycling of the amino acid alanine into glucose (gluconeogenesis). This is the most specific test for hepatocellular liver injury, although it is present in low concentrations in other tissues.
AST – (aspartate aminotransferase) is involved in metabolism of the amino acid aspartic acid. It is also sensitive for hepatocellular disease, but is less specific as it is also raised with muscle inflammation and haemolysis. High levels of liver origin suggest possible alcohol use (pyridoxine deficiency) and infiltrative liver damage (e.g. malignancy).
GGT – (gamma glutamyl transferase) is a sensitive marker of liver injury. Although induced by alcohol and some drugs (e.g. rifampicin), mild elevation is non-specific and may reflect other liver pathologies (e.g. non-alcoholic fatty liver disease).
ALP – (alkaline phosphatase) also mainly reflects hepatobiliary processes and is raised in cholestasis. ALP is not specific for liver disorders as it is produced by other tissues including bone, intestine and placenta. These sources should be considered, especially in patients with isolated elevation with concurrent elevation of GGT.
Bilirubin – is a product of red cell (haem) breakdown. Bilirubin is initially carried loosely attached to albumin as the unconjugated form. It is then taken up into hepatocytes, solubilised to form the smaller conjugated form, and excreted by the biliary system. The unconjugated form is increased by red cell breakdown (e.g. haemolysis) or reduced uptake and conjugation (e.g. Gilbert’s syndrome). The conjugated form is increased by impaired liver processing and bile flow (e.g. hepatitis, bile duct obstruction).
Total protein – the total of albumin and other plasma proteins (mostly immunoglobulins). Changes in the total protein are non specific as there may be increases and decreases in different components. For example chronic severe inflammatory liver disease may be associated with a low albumin and other liver globulins, but raised levels of immunoglobulins.
Albumin – the most abundant plasma protein, produced in adults entirely by the liver. A falling level may reflect reduced liver production, usually indicating significant liver damage, but may also reflect increased protein loss, e.g. nephrotic proteinuria, GI loss. Levels may still be normal in patients with severe acute liver damage because the half-life of albumin in plasma is about three weeks.
INR – a reflection of liver synthesis of vitamin K dependent clotting factors II, VII, IX, X. Raised INR may indicate decreased liver synthetic ability or cholestasis with reduced vitamin K absorption. Levels rise quickly with acute liver disturbance because of the short half-life of the clotting factors.
Appendix 2 – Alcohol Screening tests
The RAPS4 Alcohol Screening test for dependent drinking
Please answer these 4 questions:
During the last year, have you had a feeling of guilt or remorse after drinking?
During the last year, has a friend or a family member ever told you about things you said or did while you were drinking that you could not remember?
During the last year, have you failed to do what was normally expected from you because of drinking?
Do you sometimes take a drink when you first get up in the morning?
Alcohol Advisory Council of New Zealand ‘Drink Check’9
Your drinking will cause you or may already have caused you problems.
WOMEN
6–12 points
Medium risk
MEN
7–14 points
Your drinking is putting you at risk of developing problems
WOMEN
0-5 points
Low risk
MEN
0-6 points
Your drinking is not likely to cause you problems if it remains at this level.
Appendix 3 – Screening for hepatitis B in people not previously immune8
HBsAg
Negative
Positive
No evidence of chronic hepatitis B infection
If positive for >6 months, consistent with chronic hepatitis B infection
Investigation for Evidence of Previous Infection or Immunisation with hepatitis B8 See note a
Anti-HBs
Negative
Positive
No evidence of previous infection or immunisation
See note (b)
Compatible with previous infection or immunisation
Following a previous vaccination with documented immune response, the patient can then be presumed to be protected long term, unless they are immunosuppressed. If in doubt, revaccinate and recheck anti-HBs in 3 weeks.
A small number of patients may be positive for anti-HBc from a previous HBV infection, in the absence of anti-HBs. If there is a strong suspicion of previous infection or high risk, then order an anti-HBc.
Appendix 4 – Investigation for Evidence of Chronic HCV Infection8
Anti-HCV
Negative
Positive
No evidence of hepatitis C infection
See note (a)
Indicates possible current, previous or chronic hepatitis C infection
See note (b)
A negative test does not exclude infection within the previous eight weeks.
Positive anti-HCV is followed up by a HCV RNA test. Persistently normal LFTs and two negative HCV RNA tests 3 months apart indicate that active HCV is extremely unlikely.
Appendix 5 - Isoenzymes
In some situations, the interpretation of hepatic enzyme results may be difficult due to the occurrence of isoenzymes. These are different molecular forms of the same enzyme, which originate from different sites in the body but react in a similar manner when tested with a particular laboratory test. It is worthwhile considering other explanations for a single unexpected result.
ALP isoenzymes may originate from liver, bone, placenta, intestinal or tumour cells. Therefore elevations of ALP are often seen in children in times of bone growth (bone isoenzyme) or in pregnant women (placental isoenzyme).
ALT is the most specific liver enzyme, but occasionally originates from sources other than the liver.
AST from cardiac muscle is commonly elevated following myocardial infarction (cardiac isoenzyme). Haemolysis may also elevate AST (red blood cell isoenzyme).
GGT isoenzymes have been identified in kidney, heart and pancreas but these are not commonly encountered.
Appendix 6: Investigation for Evidence of Acute Viral Hepatitis8
ALT elevated >5 x ULN
Hepatitis A
Hepatitis B
Hepatitis C See note a
Anti-HAV IgM
Negative
Positive
No evidence of acute hepatitis A infection
Compatible with acute hepatitis A infection
Anti-HBc IgM
HBsAg
Positive
Negative
Positive
Compatible with
acute hepatitis B
infection
No evidence of
acute hepatitis B
infection
Compatible with acute or chronic hepatitis B infection
See note b
Hepatitis C cannot reliably be diagnosed in the acute phase because of the prolonged period of sero-conversion. Testing may be done for people with known risk factors. However, if HCV is negative and other causes of viral hepatitis have been ruled out, a second sample should be specifically tested for HCV one to three months later.
If HBsAg is positive for a period of greater than six months, it is consistent with chronic hepatitis B infection. Positive HBsAg represents acute HBV only if anti-HBcore IgM is also positive.
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