Liver Function Tests (LFT,s)

Definition:
Common tests that are used to evaluate liver function include:

• Albumin
• ALP
• ALT
• AST
• GGT
• PT
• Serum bilirubin

What does the liver do?

The liver is in the upper right part of the abdomen. The functions of the liver
include: storing glycogen (fuel for the body) which is made from sugars; helping
to process fats and proteins from digested food; making proteins that are essential
for blood to clot (clotting factors); processing many medicines which you may
take; helping to remove poisons and toxins from the body.

The liver also makes bile. This is a greenish-yellow fluid that contains bile acids,
bile pigments and waste products such as bilirubin. Liver cells pass bile into bile
ducts inside the liver.

The bile flows down these ducts into larger and larger ducts, eventually leading to
the common bile duct. The gallbladder is a reservoir of bile which comes off the
common bile duct. After you eat, the gallbladder squeezes bile back into the
common bile duct and down into the duodenum (the first part of the gut after the
stomach). Bile in the gut helps to digest fats.
Liver Function Tests Include:

• Alanine transaminase (ALT). This is an enzyme that helps to process

proteins. (An enzyme is a protein that helps to speed up chemical
reactions).Large amounts of ALT occur in liver cells. When the liver is injured
or inflamed (as in hepatitis), the blood level of ALT usually rises.
• Alkaline phoshpatase (ALP). This enzyme occurs mainly in liver cells
next to bile ducts, and in bone. The blood level is raised in some types of liver
and bone disease.
• Albumin. This is the main protein made by the liver, and it circulates in
the bloodstream. The ability to make albumin (and other proteins) is affected in
some types of liver disorder. A low level of blood albumin occurs in some liver
disorders.
 Total Protein. This measures albumin and all other proteins in blood.
 • Bilirubin. This chemical gives bile its yellow/green colour. A high level
of bilirubin in your blood will make you jaundiced ('yellow'). Bilirubin is made
from haemoglobin. Haemoglobin is a chemical in red blood cells that is released
when the red blood cells break down. Liver cells take in bilirubin and attach
sugar molecules to it. This is then called 'conjugated' bilirubin which is passed
into the bile ducts.
 A raised blood level of 'conjugated' bilirubin occurs in various liver
and bile duct conditions. It is particularly high if the flow of bile is
blocked. For example, by a gallstone stuck in the common bile duct, or
by a tumor in the pancreas. It can also be raised with hepatitis, liver
injury, or long-term alcohol abuse.
 A raised level of 'uncongugated' bilirubin occurs when there is
excessive breakdown of red blood cells. For example, in haemolytic
anemia.

What is liver function tests used for?

 To help diagnose liver disorders if you have suggestive symptoms (such

as jaundice). The pattern of the blood results may help to say which
disorder is causing the problem. For example, depending on which
enzyme is highest it may point to a particular disorder.
 To monitor the activity and severity of liver disorders.
 As a routine precaution after starting certain medicines to check that they
are not causing liver damage as a side-effect.

Other tests of the liver

Which may be done include:

• Blood clotting tests. The liver makes many of the proteins needed to
make blood clot. In certain liver disorders the liver cannot make enough of
these proteins and so blood does not clot so well. Therefore, blood clotting
tests may be used as a marker of the severity of certain liver disorders.

• Prothrombin time (PT):

Another measure of hepatic synthetic function is the prothrombin time.

Prothrombin time is affected by proteins synthesized by the liver. Particularly,
these proteins are associated with the incorporation of vitamin K metabolites into a
protein. This allows normal coagulation (clotting of blood). Thus, in patients who
have prolonged prothrombin times, liver disease may be present. Since a
prolonged PT is not a specific test for liver disease, confirmation of other
abnormal liver tests is essential. Diseases such as malnutrition, in which decreased
vitamin K ingestion is present, may result in a prolonged PT time. An indirect test
of hepatic synthetic function includes administration of vitamin K (10mg)
subcutaneously over three days. Several days later, the prothrombin time may be
measured. If the prothrombin time becomes normal, then hepatic synthetic
function is intact.

• Platelet count:

Platelets are cells that form the primary mechanism in blood clots. They're also the
smallest of blood cells. They derived from the bone marrow from the larger cells
known as megakaryocytes. Individuals with liver disease develop a large spleen.
As this process occurs platelets are trapped with in the sinusoids (small pathways
within the spleen) of the spleen. While the trapping of platelets is a normal
function for the spleen, in liver disease it becomes exaggerated because of the
enlarged spleen (splenomegaly). Subsequently, the platelet count may become
diminished.

• Serum protein electrophoresis:

This is an evaluation of the types of proteins that are present with in a patient's
serum. By using an electrophoretic gel, major proteins can be separated out. This
results in four major types of proteins.

These are

1) albumin,

2) alpha globulins,

3) beta globulins

4) gammaglobulins.

This test is useful for evaluation of patients who have abnormal liver function tests
since it allows a direct quantification of multiple different serum proteins. If the
gamma globulin fraction is elevated, autoimmune hepatitis may be present. In
addition a deficiency in the alpha globulin fraction can result in the diagnosis, or a
clinical clue, to A. alpha-1 antitrypsin deficiency.
 • Gamma-glutamyl transferase (GGT). This is another enzyme that
occurs in liver cells. A high level of this enzyme is particularly associated
with heavy alcohol drinking. (The liver, breaks down and clears alcohol
from the body and this enzyme is involved in the process.)

Abnormal Liver Function Tests

• Abnormal LFT,s may be asymptomatic, and are often inadequately
investigated - which may miss an early opportunity of identifying and
treating chronic liver disease
• The primary problem may be the liver or the abnormal results can be
secondary to other problems elsewhere in the body.

How to approach abnormal liver function tests

Consider drug toxicity in all cases.

Once results are obtained determine which of the following scenarios they fit in to:
Rise in bilirubin alone - need to know if unconjugated
hyperbilirubinaemia or conjugated hyperbilirubinaemia. Usually due to
defects of hepatic excretion. It can be detected by measuring the direct
bilirubin component of the total bilirubin (> 50% confirms the presence of
conjugated hyperbilirubinaemia).
Unconjugated -
o Haemolysis - Check reticulocyte count, blood film,
haptoglobins, LDH and may need direct Coomb's test.
o Drugs
o Gilbert's syndrome
o Crigler-Najjar syndrome
Conjugated -
o Dubin-Johnson syndrome
o Rotor syndrome
o Chronic liver disease, (associated with other LFT,s
abnormalities)
o Obstructive picture or cholestasis - rise in ALP and
GGT more than AST and ALT. This may be intrahepatic or
extrahepatic (bilirubin will also be raised).
Intrahepatic -
 primary biliary cirrhosis
 drugs
 Extrahepatic -
 Gallstone in common bile duct
 Head of pancreas neoplasm
 Drugs e.g. erythromycin, tricyclic antidepressants,
flucloxacillin, oral contraceptive pill and anabolic steroids
 Cardiac failure - improves with treatment
 Primary biliary cirrhosis - commoner in women and first sign
is a rise in ALP
 Primary sclerosing cholangitis
 Neoplasm - primary (rarely) and secondary
 Familial (benign)

Hepatitis picture: Rise in AST and ALT more than ALP and GGT:
• Alcohol - fatty infiltration and acute alcoholic hepatitis (usually
associated with markedly deranged liver function).
• Cirrhosis of any cause - alcohol being one of the commonest.
• Medications e.g. Phenytoin, carbamazepine, isoniazid, statins,
methotrexate, paracetamol overdose, amiodarone. (Transaminases may
be >1000 IU/l).
• Chronic hepatitis B and C.
• Acute viral hepatitis e.g. hepatitis A, B and C and CMV infection.
• Autoimmune hepatitis.
• Neoplasms - primary or secondary.
• Haemochromatosis.
• Metabolic - Glycogen storage disorders, Wilson's disease.
• Ischemic liver injury e.g. severe hypotension
• Fatty liver disease (mild elevation in transaminases <100 IU/l).
• Non-hepatic causes: Coeliac disease, haemolysis and
hyperthyroidism.

Isolated rise in individual enzymes e.g. ALP and GGT:

Isolated rise in GGT:
• This is most commonly due to alcohol abuse, or enzyme inducing
drugs.
• An isolated rise can occur even if no major liver disease.
• The rise is not related to the amount of alcohol intake.
• Also many heavy alcohol users may have normal GGT.
 • Stopping alcohol for 4 weeks should rectify the abnormality.
Isolated rise in ALP:
• Third trimester of pregnancy (comes from the placenta - a normal
finding)
• If isolated rise in ALP consider other sources e.g. bone or kidney
In the elderly consider:
o Fractures , Paget's disease of bone
o Osteomalacia
o Bony metastases
ALP is not usually raised in myeloma or osteoporosis (without a
fracture).