Interpretation of Liver Function Tests (LFTs) Flashcards
What are the 2 main reasons why LFTs are requested?
- to confirm a clinical suspicion of potential liver injury or disease
- to distinguish between hepatocellular injury (hepatic jaundice) and cholestasis (post-hepatic or obstructive jaundice)
What are the 7 components of a blood test used to assess liver function?
- alanine transaminase (ALT)
- aspartate aminotransferase (AST)
- alkaline phosphatase (ALP)
- gamma-glutamyltransferase (GGT)
- bilirubin
- albumin
- prothrombin time (PT)
- ALT, ASP, ALP and GGT are used to distinguish between hepatocellular damage and cholestasis
- bilirubin, albumin and PT are used to assess the liver’s synthetic function
If ALT and/or ALP is raised, what do you have to decide about how much it is raised by?
- if ALT is raised, decide if it is more than a 10-fold rise or less than a 10-fold rise
- if ALP is raised, decide if it is more than a 3-fold rise or less than a 3-fold rise
What is ALT a useful indicator of and why?
- ALT is found in high concentrations within hepatocytes
- ALT enters the blood following hepatocellular injury
- it is a useful marker of hepatocellular injury
What is ALP a useful clinical marker of and why?
- ALP is concentrated in the liver, bile duct and bone tissues
- it is often raised in liver pathology due to increased synthesis in response to cholestasis
- ALP is a useful indirect marker of cholestasis
How is the rise in ALT and ALP compared to determine what type of problem is present?
- a greater than 10-fold increase in ALT and a less than 3-fold increase in ALP suggests predominantly hepatocellular injury
- a less than 10-fold increase in ALT and a greater than 3-fold increase in ALP suggests cholestasis
- it is possible to have a mixed picture involving both hepatocellular injury and cholestasis
When is the level of gamma-glutamyl transferase reviewed and what may a raised GGT suggest?
- the level of GGT needs to be reviewed if there is a rise in ALP
- raised GGT can be suggestive of biliary epithelial damage and bile flow obstruction
- it can also be raised in response to alcohol and drugs (e.g. phenytoin)
- a markedly raised ALP with a raised GGT is highly suggestive of cholestasis
What would an isolated rise of ALP make you suspicious of?
- a raised ALP in the absence of a raised GGT raises suspicion of n_on-hepatobiliary pathology_
- ALP is also present in bone, so anything that leads to increased bone breakdown can elevate ALP
What are the 4 main causes of an isolated rise in ALP?
- bony metastases or primary bone tumours (e.g. sarcoma)
- vitamin D deficiency
- recent bone fractures
- renal osteodystrophy
What do blood tests typically show if a patient is jaundiced but ALP and ALT levels are normal?
an isolated rise in bilirubin is suggestive of a pre-hepatic cause of jaundice
What are the 2 causes of an isolated rise in bilirubin and what further investigations should be conducted?
- the most common cause is Gilbert’s syndrome
-
haemolysis can cause an isolated rise in bilirubin
- check a blood film, FBC, reticulocyte count, haptoglobin & LDH levels to confirm
What are the 4 main synthetic functions of the liver?
- conjugation and elimination of bilirubin
- synthesis of albumin
- synthesis of clotting factors
- gluconeogenesis
What 4 investigations can be used to assess the synthetic function of the liver?
- serum bilirubin
- serum albumin
- prothrombin time (PT)
- serum blood glucose
What is bilirubin and how does the liver process it?
- bilirubin is a breakdown product of haemoglobin
- the liver takes up unconjugated bilirubin and conjugates it
When does hyperbilirubinaemia cause clinically apparent jaundice?
- hyperbilirubinaemia does not always cause clinically apparent jaundice
- it is usually visible when bilirubin > 60 umol/L
What symptoms and signs that the patient has can distinguish whether there is conjugated or unconjugated hyperbilirubinaemia?
- unconjugated bilirubin is NOT soluble in water
therefore, it does NOT affect the colour of the patient’s urine
- conjugated bilirubin is water soluble and can pass into the urine as urobilinogen
this causes the urine to become darker in colour
How can the colour of stools be used to differentiate the causes of jaundice?
- if bile and pancreatic lipases cannot reach the bowel due to a blockage (e.g. in obstructive post-hepatic pathology)
- this means that fat is not able to be absorbed
- this results in stools that are more pale, bulky and difficult to flush
How can the combination of the colour of urine and stools given an indication as to what type of jaundice might be present?
- normal urine + normal stools = pre-hepatic cause
- dark urine + normal stools = hepatic cause
- dark urine + pale stools = post-hepatic (obstructive) cause
What are the 3 most common causes of unconjugated hyperbilirubinaemia?
- haemolysis (e.g. haemolytic anaemia)
- impaired hepatic uptake (e.g. drugs, congestive cardiac failure)
- impaired conjugation (e.g. Gilbert’s syndrome)
What are the 2 most common causes of conjugated hyperbilirubinaemia?
- hepatocellular injury
- cholestasis
What is the role of albumin?
- it is synthesised in the liver
- it helps to bind water, cations, fatty acids and bilirubin
- it plays a role in maintaining the oncotic pressure of the blood
For what 3 reasons might albumin levels fall?
- liver disease resulting in decreased production of albumin (e.g. cirrhosis)
- inflammation triggering an acute phase response which temporarily decreases the liver’s production of albumin
- excessive loss of albumin due to protein-losing enteropathies
What is prothrombin time (PT)?
it is a measure of the blood’s coagulation tendency, specifically assessing the extrinsic pathway
What can an increased PT time indicate and why?
- it can indicate liver disease and dysfunction in the absence of anticoagulant use and vitamin K deficiency
- the liver is responsible for the synthesis of clotting factors
- hepatic pathology impairing this process can result in increased PT time
What does the AST / ALT ratio tell you about the functioning of someone’s liver?
- the AST / ALT ratio is used to determine the likely cause of LFT derangement
- ALT > AST is associated with chronic liver disease
- AST > ALT is associated with cirrhosis and acute alcoholic hepatitis
What is gluconeogenesis?
the metabolic pathway that results in the generation of glucose from certain non-carbohydrate carbon substances
the liver plays a significant role in gluconeogenesis
Why is serum blood glucose measured as part of an LFT?
- the liver plays a significant role in gluconeogenesis
- measuring serum blood glucose provides an indirect assessment of the liver’s synthetic function
- gluconeogenesis tends to be one of the last functions to become impaired in the context of liver failure
What would you expect ALT, ALP, GGT and bilirubin levels to be like in acute hepatocellular damage?
- ALT is significantly raised
- ALP is normal or slightly raised
- GGT is normal or slightly raised
- bilirubin is raised or significantly raised
What would you expect the levels of ALT, ALP, GGT and bilirubin to be in chronic hepatocellular damage?
- ALT is normal or slightly raised
- ALP is normal or slightly raised
- GGT is normal or slightly raised
- bilirubin is normal or slightly raised
What would you expect the levels of AST, ALP, GGT and bilirubin to be like in cholestasis?
- ALT is normal or slightly raised
- ALP is significantly raised
- GGT is significantly raised
- bilirubin is significantly raised
What are the most common causes of acute hepatocellular injury?
- poisoning (paracetamol overdose)
- infection (hepatitis A or B)
- liver ischaemia
What are the 4 most common causes of chronic hepatocellular injury?
- alcoholic fatty liver disease
- non-alcoholic fatty liver disease
- chronic infection (hepatitis B or C)
- primary biliary cirrhosis
What are the 3 less common causes of chronic hepatocellular injury?
- alpha-1 antitrypsin deficiency
- Wilson’s disease
- haemochromatosis
