Liver function tests

Question 1

What does a conventional Liver function test profile include?

Answer 1

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

Question 2

Why are LFTs requested?

Answer 2

 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

Question 3

What types of bilirubin can be measured in the blood?

Answer 3

conjugated and unconjugated

Question 4

describe Unconjugated hyperbilirubinaemia

Answer 4

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

Question 5

Describe conjugated hyperbilirubinaemia

Answer 5

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

Question 6

What are aminotransferases?

Answer 6

Include aspartate (AST) and alanine aminotransferase (ALT)

• markers of hepato-cellular injury

Question 7

What is the function of aminotransferases?

Answer 7

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

Question 8

Describe AST

Answer 8

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

Question 9

Describe ALT

Answer 9

 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

Question 10

What is ALP?

Answer 10

 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

Question 11

Why is ALP raised in liver diseases?

Answer 11

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)

Question 12

What liver disease is ALP raised in?

Answer 12

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.

Question 13

What is γ – Glutamyl transferase (GGT)?

Answer 13

Microsomal enzyme (intracellular)

Responsible for the transfer of glutamyl groups from gamma-glutamyl peptides to other peptides or
amino acids

Question 14

Where is γ – Glutamyl transferase (GGT) found?

Answer 14

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.

Question 15

What is the use of γ – Glutamyl transferase (GGT) as a lifer function test?

Answer 15

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.

Question 16

What is the link between GGT and alcohol consumption?

Answer 16

 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

Question 17

Why is GGT not used in population screening?

Answer 17

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

Question 18

What proteins can be tested to investigate the function of the liver?

Answer 18

 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

Question 19

What are the stigmata of chronic liver disease?

Answer 19

Spider nevi
Palmar erythema
Caput medusae – (palm tree sign) appearance of distended and engorged superficial epigastric
veins

Question 20

What signs of liver disease can be found on physical examination?

Answer 20

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

Question 21

What is Elevation of transaminases indicative of?

Answer 21

Hepatocellular injury

(Remember that these are intracellular enzymes, and
an increase therefore indicates increased cell
breakdown)

Question 22

What is elevation of alkaline phosphatase and γ-gt indicative of?

Answer 22

Cholestasis

Question 23

What is Elevation of bilirubin indicative of?

Answer 23

Hepatocellular injury or cholestasis

Haemolysis also possible

Question 24

How can liver disease be classified?

Answer 24

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.

Question 25

Which tests are most useful in distinguishing between hepatocellular and cholestatic disease?

Answer 25

The AST, ALT, and alkaline phosphatase tests

Question 26

Which tests are most useful measures of liver cell injury?

Answer 26

ALT and AST

Question 27

What are non-liver causes of raised AST?

Answer 27

acute injury to cardiac or skeletal muscle.

Question 28

What are the LFTs like in Diseases that primarily affect hepatocytes?

Answer 28

such as viral hepatitis

cause disproportionate elevations of the AST and ALT levels compared with the alkaline phosphatase level.

Question 29

Describe the LFT pattern of Acute alcoholic hepatitis

Answer 29

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

Question 30

Describe the LFT pattern of viral hepatitis

Answer 30

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

Question 31

What is the LFT pattern of Autoimmune hepatitis (AIH)

Answer 31

is characterized by very high serum aminotransferase (ALT and AST) levels

Question 32

Describe the LFT pattern of Primary Biliary Cirrhosis (PBC)

Answer 32

is a cholestatic disorder with predominant elevations of the alkaline phosphatase level.

Question 33

What is the LFT pattern of Non-Alcoholic Fatty Liver Disease?

Answer 33

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.

Question 34

Describe the hepatocellular pattern of abnormal LFTs

Answer 34

 ALT or AST elevated (> 150 U/L)

 ALP usually not significantly elevated (< 200 U/L)

Question 35

Describe the cholestatic pattern of abnormal LFTs

Answer 35

 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