Liver function tests Flashcards
What does a conventional Liver function test profile include?
o Bilirubin o Albumin o Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) o Alkaline phosphatase o Gamma glutamyl transferase (γ-GT) >NB: this has to be requested separately o Total protein
Why are LFTs requested?
Screening of healthy people
To investigate unexplained symptoms
o Include or exclude a potential liver disorder
To investigate symptoms and signs suggestive of liver disease
For pre-operative or baseline assessment
To monitor the progress of established liver disease and assess the response to treatment
What types of bilirubin can be measured in the blood?
conjugated and unconjugated
describe Unconjugated hyperbilirubinaemia
o Also referred to as indirect bilirubin
o Hyperbilirubinaemia when it comprises >85% of total bilirubin
o Occurs with increased bilirubin production or defects in hepatic uptake or conjugation of
bilirubin
Problem with uptake or conjugation
o Gilbert’s disease
Describe conjugated hyperbilirubinaemia
o Occurs with inherited or acquired defects in hepatic excretion
Problem with excretion
o Referred to as direct bilirubin
o Hyperbilirubinaemia when it comprises >50% of total bilirubin measured with disease
What are aminotransferases?
Include aspartate (AST) and alanine aminotransferase (ALT)
- markers of hepato-cellular injury
What is the function of aminotransferases?
Participate in gluconeogenesis
o Catalyse the transfer of amino groups from aspartic acid or alanine to ketoglutaric acid to
produce oxaloacetic acid and pyruvic acid respectively
Describe AST
Present in cytosolic and mitochondrial isoenzymes
o Intracellular enzyme – in order for this enzyme to be expressed/measured at a high level in the
periphery there must be breakdown of cells (i.e. hepatocellular injury)
Not specific to the liver
o Present in liver, cardiac and skeletal muscle, kidneys, brain, pancreas, lungs, leukocytes and red
cells
o AST was previously used as a cardiac marker to identify MI
o Can increase significantly with rhabdomyolosis (muscle damage) may be very high in e.g.
marathon runners due to muscle breakdown
Less sensitive and specific for the liver
Plasma half-life 48 hours
o Need to wait at least 48 hours before measurement to observe difference
Describe ALT
Cytosolic enzyme
Similar tissue distribution as AST but in extrahepatic tissues the activity is much lower
o More specific to the liver than AST
Increase of ALT is more specific for liver disease
Plasma half-life 18 hours
Remember: ALT is more specific to the Liver than AST. AST is more Systemic in distribution
What is ALP?
ALP group of enzymes that hydrolyse phosphate esters in alkaline solutions
o NB: physiological substrate is not known!
Not specific to the liver, different isoenzymes
o Also found in bones
Why is ALP raised in liver diseases?
The liver derived isoenzyme is located on the exterior surface of the bile canalicular membrane
o Probably enters the bloodstream via the paracellular pathway
o Therefore, diseases that predominately affect hepatocyte secretion (e.g., obstructive diseases)
will be accompanied by elevations of alkaline phosphatase levels (predominant over
transaminase level elevations)
What liver disease is ALP raised in?
ALP is elevated in obstructive type liver disease, e.g bile duct obstruction.
o It is not related to failure to clear ALP or release from damaged hepatocytes
o More likely by stimulated synthesis.
What is γ – Glutamyl transferase (GGT)?
Microsomal enzyme (intracellular)
Responsible for the transfer of glutamyl groups from gamma-glutamyl peptides to other peptides or
amino acids
Where is γ – Glutamyl transferase (GGT) found?
Present throughout the liver and hepatobiliary tree
o Also found in other organs (heart, kidneys, lungs, pancreas and seminal vesicles)
o However, plasma activity is mostly related to the liver isoenzyme.
What is the use of γ – Glutamyl transferase (GGT) as a lifer function test?
Poor specificity for liver disease, but very useful when used in combination with alkaline phosphatase
measurements
o Useful to identify raised ALP of liver origin or chronic alcohol consumption
Used to determine the reason for elevated serum alkaline phosphatase (ALP)
Both ALP and GGT are elevated in disease of the bile ducts and in some liver diseases, but only ALP will be
elevated in bone disease.
If the GGT concentration is normal in a person with a high ALP result, the cause is most likely to be bone
disease.
What is the link between GGT and alcohol consumption?
raised GGT in patients with chronic liver disease may be due to induction of the enzyme by the alcohol and/or because of the liver damage
If raised, diligently enquire about possible alcohol abuse
However, increased GGT cannot simply be attributed to alcohol abuse
o There is no relation between level of GGT and amount or duration of alcohol consumption
o Alcoholic patients without liver disease - only half will have raised GGT
Will fall to normal after at least 8 weeks of abstinence
Why is GGT not used in population screening?
o False positive can occur because of enzyme inducing drugs (e.g. phenytoin, carbamazepine and
barbiturates)
Stop medication and redo test
o False negative occurs in those who do not have liver disease
What proteins can be tested to investigate the function of the liver?
Albumin (17-20 day half-life) is the most important protein produced
Prothrombin time (PT) measures the rate of conversion of prothrombin to
thrombin and thus reflects a vital synthetic function of the liver
o Can be used to detect paracetamol overdose
Alpha-1- AT is routinely measured to assess for liver function
o When defective can build up in the liver, causing cirrhosis
What are the stigmata of chronic liver disease?
Spider nevi
Palmar erythema
Caput medusae – (palm tree sign) appearance of distended and engorged superficial epigastric
veins
What signs of liver disease can be found on physical examination?
Body mass index
Nutritional status
Jaundice
Stigmata of chronic liver disease
Ascites, pleural effusion, ankle oedema = indicate defect in albumin synthesis
Hepatomegaly, splenomegaly, other abdominal masses
What is Elevation of transaminases indicative of?
Hepatocellular injury
(Remember that these are intracellular enzymes, and
an increase therefore indicates increased cell
breakdown)
What is elevation of alkaline phosphatase and γ-gt indicative of?
Cholestasis
What is Elevation of bilirubin indicative of?
Hepatocellular injury or cholestasis
Haemolysis also possible
How can liver disease be classified?
o Hepatocellular - primary injury is to the hepatocytes
o Cholestatic - primary injury is to the bile ducts;
o Infiltrative - the liver is invaded or replaced by non-hepatic substances, such as neoplasm or
amyloid.
Which tests are most useful in distinguishing between hepatocellular and cholestatic disease?
The AST, ALT, and alkaline phosphatase tests
Which tests are most useful measures of liver cell injury?
ALT and AST
What are non-liver causes of raised AST?
acute injury to cardiac or skeletal muscle.
What are the LFTs like in Diseases that primarily affect hepatocytes?
such as viral hepatitis
cause disproportionate elevations of the AST and ALT levels compared with the alkaline phosphatase level.
Describe the LFT pattern of Acute alcoholic hepatitis
pattern of liver test abnormality is hepatocellular
o The AST level is higher than the ALT level, and the ratio is greater than 2:1
Describe the LFT pattern of viral hepatitis
o most often produces a hepatocellular pattern of injury
o AST and ALT level elevations predominate
o Asymptomatic patients with normal aminotransferase levels may still be infected
What is the LFT pattern of Autoimmune hepatitis (AIH)
is characterized by very high serum aminotransferase (ALT and AST) levels
Describe the LFT pattern of Primary Biliary Cirrhosis (PBC)
is a cholestatic disorder with predominant elevations of the alkaline phosphatase level.
What is the LFT pattern of Non-Alcoholic Fatty Liver Disease?
NAFLD is the most common cause of mildly elevated liver enzymes.
o Liver tests are unreliable guides to the presence or absence of fatty liver disease.
o When elevated, enzymes show hepatocellular pattern, often with an AST/ALT ratio of less than 1.
o However, they can be normal.
Describe the hepatocellular pattern of abnormal LFTs
ALT or AST elevated (> 150 U/L)
ALP usually not significantly elevated (< 200 U/L)
Describe the cholestatic pattern of abnormal LFTs
Characterised by very high ALP (> 180 U/L)
ALT is not usually significantly elevated (< 150 U/L) and neither is GGT (> 100 U/L)
Sometimes a small increase in bilirubin, but not exceeding < 50 umol/L
