ALT (Alanine Aminotransferase)
What is ALT?
ALT is short for alanine aminotransferase. This is the most useful
enzyme test in the assessment of hepatitis. It was once referred to
as SGPT and sometimes in North America this term is still used.
The liver is virtually the only place in the body in which ALT is found
and the level of ALT in the bloodstream indicates the amount of ALT
that is spilled out from the liver during the breaking down of liver
cells. This occurs in all of us and levels between 0 and 55 units/litre
are often found (variations occur with different pathology laboratories).
It is important to remember that ALT levels can fluctuate over a short
period of time. Samples taken only hours apart, can vary significantly,
even though there may not be any significant change in the health of
the liver between tests.
The ALT level is usually higher than the AST (another liver enzyme).
There can be many reasons for elevated ALT levels, such as regular,
heavy alcohol consumption which in itself can cause liver inflammation.
In patients with alcoholic liver disease and in patients with cirrhosis,
the ALT is usually lower than the AST.
ALT is used often as a rough guide to the amount of liver inflammation.
It is imperfect as some patients can have a normal ALT and a lot of
inflammation and other patients can have a high ALT and not much inflammation.
In general, however, the higher the ALT, the more liver inflammation
there is.
There is no “typical” ALT reading for an individual with
hepatitis C. At present, ALT levels need to be above the upper limit
of the normal range in order for an individual to qualify for government
funded Interferon treatment. Participation in clinical trials related
to hepatitis C treatment also requires ALT levels to be above normal.
Anyone with raised ALT – especially if the ALT is above 50 on
a number of occasions should discuss with their doctor whether they
should be referred to a liver clinic for a full liver assessment. A
liver specialist can then establish what is causing the elevation in
ALT and discuss appropriate treatment options.
UPPER ABDOMINAL ULTRASOUND
What is an Ultrasound Examination?
An ultrasound examination is a painless investigation to look at various
organs within the body.
From the point of view of liver disease, the ultrasound is designed
to examine the liver, bile ducts, pancreas, gallbladder, spleen and
often the veins of the portal system. Occasionally other areas may be
the focus of the examination.
The ultrasound exam involves the passage of high frequency sound waves
through the skin and these are reflected, to differing degrees, by the
internal organs and structures.
Preparation for the Ultrasound
You will usually be asked to have nothing by mouth for 6 hours prior
the examination. Clear fluids are an exception and it is alright to
have these up to the time of the examination. Remember, however, no
milk.
How is the Test done?
You will be taken into the room with the ultrasonographer. Patients
usually lie in a comfortable position, which allows the technician to
examine the area needing investigation. The room will be slightly darkened
and a screen with the ultrasound image will be beside the bed.
Some clear gel will usually be put on your skin over the area being
examined. This helps the transmission of sound waves through the skin.
The examination itself should cause no pain but if the area over the
examination is performed is tender, it will, of course, be uncomfortable.
Certainly if the doctor or technician has to press more firmly in order
to obtain a clear picture, there may be some discomfort.
The examination usually takes between 10 and 40 minutes.
After the Test
You will be able to go home immediately after the test. You will be
able to drive your car and resume eating and drinking.
LIVER BIOPSY
What is a Liver Biopsy?
Liver biopsy is a diagnostic procedure used to obtain a small amount
of liver tissue, 
approximately
1-2cm long and 1-2mm wide. This can be examined under a microscope
to
help identify the cause of liver problems or the severity of liver
damage.
How is a Liver Biopsy performed?
The most common way a liver sample is obtained is by inserting a needle
into the liver for a second or so. This is usually done under x-ray
control in a Radiology Department or Hospital and the patient is frequently
sent home within 3-6 hours of the procedure, if there are no complications.
The Radiologist performing the procedure determines the best site,
depth and angle of the needle puncture by the use of ultrasound (or
occasionally CT scanning).
The skin and the area under the skin are anaesthetised and the needle
is passed quickly into and out of the liver.
Approximately a third of patients have no or very little pain afterwards,
while the rest experience localised pain over the site of the injection
or pain up in the right shoulder. This usually lasts only half an hour
or so but can be more prolonged.
When is a Liver Biopsy useful?
Liver biopsy is often used to diagnose the cause of chronic liver disease.
It is also used to diagnose the cause liver lump or mass that can
be difficult to diagnose by less invasive techniques. In many cases
the specific cause of the chronic liver disease is known or strongly
suspected but a liver biopsy is used to confirm the diagnosis as well
as determining the amount of damage to the liver.
This can guide advice with respect to lifestyle changes, options with
treatments and also gives an idea as to the likely cause of the liver
disease.
What are the dangers of Liver Biopsy?
The primary risk of Liver Biopsy is bleeding from the site of needle
entry into the liver. Most people bleed a little after the procedure,
but significant bleeding occurs in less than 1 in 100 patients.
Complications involving the puncture of other organs are a lot less
likely under ultrasound. Occasionally there can be a collection of blood
under the liver capsule (called a sub-capsular haematoma). This may
result in prolonged discomfort in the right upper part of the abdomen.
It is stated that moderately prolonged pain – for several days
or so, does occur after Liver Biopsy in about 6% of patients.
Fortunately
the risk of death from Liver Biopsy is extremely low.
In order to reduce the risk of significant bleeding, the coagulation
or clotting status is checked by blood test in all patients prior to
a biopsy.
If the prothrombin time – a coagulation test, is too high, a
standard biopsy is not recommended. Options in this situation include
a biopsy via the jugular vein or the use of vitamin K or plasma concentrate
(fresh frozen plasma) to correct the clotting abnormalities.
What will happen after the Liver Biopsy?
Following the biopsy, you will be observed for several hours to ensure
there is no severe pain o;r evidence of excessive bleeding. You will
then be allowed to go home. Patients are advised to rest for the remainder
of the day.
HEPATITIS C VIRUS (HCV) ANTIBODY TEST
What is a HCV antibody test?
The initial screening test for hepatitis C is a blood test. This is
called an antibody test.
With informed consent, a sample of blood is taken and sent to a laboratory
to be tested.
What does the test look for?
This test is used to detect the presence of antibodies to the hepatitis
C virus in your blood. The result of this test can be either negative
(which means NO antibodies have been detected) or positive (which means
antibodies HAVE BEEN detected).
After infection, it can take up to 6 months before antibodies to the
virus can be detected. This is known as the “window period”.
During this time it is possible to get a false negative result. It is
also possible to transmit the hepatitis C virus during this period.
A positive result means that you have been exposed to the virus and,
in the majority of cases; 15 – 20% of people who are exposed to
the virus clear it naturally within 6 months of exposure, but the majority
(80% - 85%) remain infected.
The HCV antibody test does not indicate the amount of liver damage
that may have been caused.
The antibody test is usually free under Medicare. In some states and
territories, sexual health clinics also provide this service.
Sometimes the result can be indeterminate or unclear. In this case,
a PCR test should be conducted (in these circumstances, the PCR test
is rebatable under Medicare).
Babies born to mothers with hepatitis C will have maternal antibodies
which usually disappear after about 18 months. A positive antibody test
after this time may indicate that the child has been exposed to the
virus. A PCR test would be useful at this stage to determine if the
infection is active or not.
Who is notified of a positive result?
Hepatitis C is a notifiable disease. This means that it is a legal
requirement in most states and territories (Western Australia is the
exception) that testing laboratories send all positive test results
to the relevant health department.
This information is used for statistics only. Health departments are
bound by law to keep personal information (i.e. names and addresses
and other identifying details) confidential.
PCR TEST
What is a PCR test?
PCR stands for polymerase chain reaction. It is a laboratory technique
that amplifies the virus genetic material, present in the blood to
a
level that can be detected. As far as the hepatitis C virus is concerned,
PCR (more correctly called HCV.RNA) can provide three levels of information:
Presence or absence of virus genetic material in the blood.
This is called the qualitative hepatitis C PCR and its result is
expressed as either negative or positive.
A positive result means that a person
can pass the virus on to others through blood to blood contact. A negative
result means that the virus was not detected in the blood. The virus
may have been eradicated or there may be very low levels of virus,
undetectable by the PCR test.
Level of virus (or viral load) in the blood. This is called quantitative
hepatitis C PCR and its results are expressed in million of copies
of
virus genetic material per ml of blood or international units per ml
of blood.
What does the PCR test involve?
With informed consent, a sample of blood is taken and sent to a laboratory
to be tested.
What are the costs of these tests?
The quantitative and genotyping PCR usually form part of the initial
assessment process for someone who is considering treatment for hepatitis
C. They can be part of the treatment package and therefore of no cost
to the patient.
The qualitative hepatitis PCR test is rebatable under Medicare under
certain conditions. Your local GP will be able to advise you of the
costs involved in each of these tests.
For further information contact the Australian Hepatitis C Council
who have produced a booklet “Preparing for Testing”. The
booklet is available from the Council.
GENOTYPES
What does the term genotype mean?
Genotype refers to the genetic make-up of an organism or a virus. There
have been at least six distinct HCV genotypes identified.
HCV is an RNA virus related to the Flavivirus family. RNA viruses are
genetically less stable than DNA viruses and are prone to mutate during
replication.
It is a common misconception that hepatitis C is just one virus. In
reality (as a result of mutation over hundreds of years), it is a group
of very closely related strains of virus. They are similar enough to
be 
called HCV, but based on genetic differences, they can be classified
into distinct groups called genotypes.
Can people become infected with different genotypes?
Yes. Previous or current infection with one genotype or strain of hepatitis
C does not protect against reinfection with the same or different genotypes
of the virus.
Subtypes
Within each genotype, there is further difference between viruses –
too small to be seen as a new genotype but significant enough and measurable,
thus forming HCV subtypes.
These lesser classifications are described as HCV subtype 1a or 1b,
2a or 2b etc.
What is a Quasispecies?
As the virus continues to replicate in each person, there is the potential
for quasispecies to form. Quasispecies are very closely related mutations
of the original virus.
Over time, the diversity of quasispecies increases and may affect response
to treatment.
What are the most common genotypes in Australia
35% of people with hepatitis C have subtype 3 (mostly being 3a)
35% have 1a
15% have 1b
7% have subtype 2
The remaining people have other genotypes
Do genotypes play a role in the progression
of HCV?
This is still a controversial area, requiring further research. A large
study by Poynard et al assessed factors associated with fibrosis progression
in 2,235 patients. No definite link was found between genotype and fibrosis
progression.
How does genotype affect HCV treatment?
Research has shown that people with genotypes 2 or 3 have a higher
SVR (sustained response rate) to combination therapy
with Interferon and Ribavirin (60 – 70%)
than genotypes 1 (20 – 30%).
However other factors such as stage of fibrosis, age, duration of infection,
viral load, gender and alcohol consumption also influence response to
treatment.
The duration of treatment is also influenced by genotype. Generally,
people with genotype 1 are treated with combination therapy for 12 months.
People with genotype 2 or 3 are generally treated for 6 months.
Other factors, such as the degree of fibrosis can also influence the
duration of treatment.
How is the genotype determined?
This requires laboratory analysis of a blood sample. The genotype test
is rebatable under Medicare if it is being done as part of an assessment
for hepatitis C treatment. If not, check with your doctor as to the
possible costs involved.
