The presence of hepatitis C virus in the blood is detected with a PCR test on blood samples. Many people will be given a screening test before the PCR test. This screening test is the hepatitis C antibody test.
Hepatitis C Antibody Test
This is the hepatitis C screening test which shows whether you have ever come into contact with the virus. It looks for hepatitis C antibodies produced by your body to fight against the virus. The antibody test returns results of “positive”, “negative” or “indeterminate”. The hepatitis C antibody test is simply a marker of past exposure.
Positive result: This means you have been infected with the hepatitis C virus before and your body has produced antibodies to the virus. It does not indicate whether or not you still have the virus. For every 100 people who are exposed to the hepatitis C virus 25 or so clear the virus. Clearing the virus the person is no longer infected and is not infectious but will remain antibody positive for some years. After that the antibody may disappear gradually. Occasionally a false positive result may occur, usually in people who have certain disease such as autoimmune disease, malignancies of blood forming tissues.
Negative result: This means you have not been infected with the hepatitis C virus, unless you have been exposed to the virus recently and have been tested in the “window period”. This is the time it takes for the body to develop antibodies after exposure to the hepatitis C virus. The window period is between three to six months. This test is very reliable but not 100%.
A false negative result may be due to:
- limits in technology
- testing done during the window period. Most people (90%) who have been exposed to the virus will produce antibodies within 3 months from exposure. This means that 10% of people have not become antibody positive in 3 months, it will take them longer and they'll need a repeat test after a further 3 months.
- Other illnesses that prevent the production of enough antibodies for the test to measure. Where there is any doubt about a person's ability to make antibodies, they should have supplementary tests such as a PCR test (see section on PCR test).
Indeterminate result: This is when the result is not clearly negative or positive. In South Australia all antibody positive results are repeated using a different test kit. Indeterminate results are usually weakly positive on one test and negative on the second. There are three possible explanations:
- Sero-converting - the person is in the process of becoming Hepatitis C antibody positive, but hasn't quite got there yet. The test should be repeated in a month or two and will usually be positive by then if you have the virus. A PCR test will clarify the result.
- False result - because of other disease, such as auto-immune disease or certain blood disorders, there is a cross reactivity with the Hepatitis C antibody test. This person does not have Hepatitis C. Often on repeat testing it will remain indeterminate. A PCR test should be performed to look for the virus itself (See PCR testing).
- Losing the antibody - A person who clears the virus, whether after initial infection or as a result of treatment, may eventually lose their antibodies. This process can take months or years and during that time they may be indeterminate. Again, repeat testing for antibodies and a PCR test for the virus should clarify things.
PCR tests (Polymerase Chain Reaction)
Also known as hepatitis C PCR, viral RNA test and hepatitis C RNA test, PCR tests look for actual virus in the blood. The Hepatitis C virus is an RNA virus (we on the other hand have DNA in our chromosomes). In contrast to the antibody test which is indirect (that is virus enters the body which creates antibodies thus the antibodies infer the presence of Hepatitis C virus), the PCR test looks for bits of the virus itself. PCR testing is technologically difficult and very easily contaminated, so tests should be done on a fresh blood specimen which has not already been tested. The test amplifies up the tiny amounts of virus, which are present in the blood of an infected person. In the early days, there were major problems with quality of PCR tests and variability between laboratories. It is much more reliable nowadays but as always, no test is 100% fail safe and results need to be looked at in context and with a critical eye. There are three types of PCR. Qualitative simply detects if the virus is present, quantitative detects how much virus is present and genotype detects which kind of hepatitis C virus.
What the results mean
Hepatitis C PCR positive/Hepatitis C RNA positive means there is detectable virus in the blood. Positive results are usually very reliable. By definition this means the person has active disease; they are infected and infectious. PCR negative means that there is no detectable virus in the blood and can have a number of possible meanings such as:
- Low amount of virus - a negative PCR may mean that there was simply not enough virus to measure. The test has a minimum threshold below which virus is not detectable even though it is present. During the course of Hepatitis C infection the amount of virus in the blood fluctuates (goes up and down) however it is rare to have repeatedly negative PCR tests in active infection - so two negative PCRs one year apart, with normal liver functions, normally means that the virus is gone.
- Treatment Response - During interferon treatment, the Hepatitis C virus may disappear. Unfortunately for some people as soon as treatment stops, the virus comes right back. Obviously it was there all the time but just not enough to measure. For the lucky ones, the virus will not come back, but a cure cannot be assumed until the PCR has been negative for some years.
- Clearance or Cure - A negative PCR means no measurable virus in the blood. A negative PCR can mean, of course, that there is no virus present in the blood or body. Some people clear the virus after the initial infection and some as a result of treatment. Because of limits to our technology it is necessary to have more than one negative PCR before it can be thought to be gone altogether.
Current Medicare PCR criteria: If you have normal liver function for two consecutive tests, six months apart, you are eligible to have a Medicare covered PCR test. Indeterminate antibody test (as outlined above) means you can have a free PCR test. Immunosuppressed - if you have HIV infection or certain chronic diseases such as kidney disease, then you may not be able to produce adequate antibodies and can have a free PCR test. Certain cases of acute infection where a PCR may change clinical management, e.g. after needlestick injury. PCR tests are also used extensively to assess treatment needs, response and follow up. These tests (which may include quantitative and genotype PCRs) are only available in specialist centres (treating hospitals).
Liver Function Test
Liver Function Tests (LFTs) are used for the ongoing monitoring of hepatitis C positive people. There are two aspects to liver function testing. The first is signs of liver injury. When liver cells are damaged or killed the enzymes, that exist inside the cell to do work, leak out into the blood stream. We can measure this. Because cells are dying and being replaced constantly, there is a little of the enzyme in your blood all the time. The amount present goes up when the liver is being injured by viral infection, toxic chemicals or alcohol, etc. These enzymes (known as transaminases) have a 'normal range'. It is only when the amount present exceeds the normal range that it clearly indicates ongoing liver damage. To complicate the issue, some people with normal liver enzymes (LFTs) also have ongoing damage. Signs of liver failure can also be observed through blood tests results.
ALT (Alanine-aminotransferate) is the marker of hepatitis C. In a hepatitis C positive person any elevation of ALT means active disease. Unfortunately the relationship between ALT and the amount of liver damage you have is weak, so you can have quite serious liver injury with only a mild elevation of ALT, or even a normal ALT reading There are three patterns of enzymes in hepatitis C virus, continually elevated readings, around 50 - 200 or so, fluctuating readings, when you have a blood test it may sometimes be normal and sometimes be elevated (for interferon treatment eligibility you need three elevated ALT tests within a six month period, to achieve this you can have blood tests done once or twice weekly if need be) and continuously normal. AST (aspartate aminotransferase) is often raised a little; usually lower than ALT. This has no particular significance.
GGT(gamma-glutamyl transpeptidase) is the liver enzyme that has been traditionally used as a marker of excess alcohol intake. If your GGT is up at all, you should consider giving up alcohol altogether whilst you are infected with hepatitis C. People with elevated GGT tend not to respond well to interferon. If GGT is over 100 or so, it can also be associated with gastro-intestinal symptoms (nausea, bloating, appetite disturbance and wind). Some people also have itching of the skin, the result of impairment to bile flow associated with bile duct damage, which is reflected in the elevated GGT. Your doctor can measure your bile acid levels and type on a regular blood specimen. These symptoms may be alleviated by the use of a medication called urso-deoxycholic acid (USDA), which is a 'friendly' bile acid and protects your bile ducts from ongoing damage. This medication is available on application to the 'special access drug scheme'. Your GP should discuss the matter with a liver specialist.
Other liver tests
In routine hepatitis C all other liver tests should be normal. If you have abnormalities then you should be in the care of a specialist who can work with your GP.
Other Blood Tests
Over 6 - 12 months you should have a number of other blood tests. These aim to screen you for other causes of liver disease; make sure you do not have; or are vaccinated against other liver toxic viruses; review your immune system, blood clotting and nutritional status.
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