- Tests to diagnose hepatitis C
- Routine blood tests
- Hepatitis C viral load (RNA testing)
- Hepatitis C tests and what the results mean
- Hepatitis C genotype
- Predominant hepatitis C genotype by region
- Liver enzyme tests: ALT and AST
- Other liver enzymes: ALP, GGT, bilirubin, albumin and prothrombin time
- Screening for liver cancer in people with cirrhosis
- Lab results record sheet
- Lab results: reference ranges for men and women
- Liver biopsy
- When is a biopsy important?
- Interpreting biopsy results
- Alternatives to a biopsy: non-invasive biomarkers of liver disease
HCV testing is recommended annually for HIV-positive people especially if diagnosed with another STI and/or aresexually active. It is also recommended after confirmed abnormal liver enzymes.
Although you may have already been diagnosed with HIV and HCV, information on how HCV is diagnosed is important.
HCV testing is a two-stage process. The first test is usually an HCV antibody test. If it is positive, it means that you have been infected with hepatitis C in the past, and that you may still be infected.
People who have spontaneously cleared hepatitis C without treatment remain antibody-positive for years afterwards. On the other hand, antibody test results may be negative even when someone does have chronic hepatitis C. This may occur when:
- CD4 cell count is low (less than 200), because the immune system may not be producing antibodies.
- In acute (early) HCV infection, since antibodies take 6 to 24 weeks after infection before they develop.
An HCV viral load test (RNA) will confirm or rule out chronic infection. The viral load test looks for genetic material of HCV in the same way as an HIV viral load test detects HIV.
If you have detectable HCV viral load, it means that you are currently infected with HCV. If your hepatitis C viral load is undetectable, a second test should be done six months later. If two successive test results are undetectable, you have cleared HCV.
After these test show you have HCV, your clinic should run a series of other blood tests.
These include HCV genotype, testing for hepatitis A and B, full blood count (FBC) and clotting studies, liver enzyme tests (including ALT, AST, albumin and GGT), thyroid function test (TFT), serum iron, liver autoantibodies, and liver ultrasound.
The hepatitis C (HCV) virus replicates at a much greater rate than HIV (trillions vs. millions copies per day) so HCV viral load is often high -- sometimes in the tens of millions.
People with HIV usually have higher hepatitis C viral loads than people with HCV alone.
Unlike HIV, hepatitis C viral load is not related to the risk of the disease getting worse. Unlike HIV, the hepatitis C viral load is not used to decide when to start treatment. This can be confusing, especially if you are used to using HIV viral load results as a guide for when to start HIV treatment.
HCV treatment is more effective for people who start treatment when their HCV viral load is low (less than 400,000 IU/mL), but most people already have viral loads that are well above this before treatment.
About HCV viral load testing
HCV viral load is measured in International Units per millitlitre (IU/mL). It is measured from a blood sample.
There are two types of viral load tests.
HCV antibody test result
Alanine aminotransferase (ALT: a liver enzyme)
Undetectable on two tests, performed at least six months apart
May be up to 7 fluctuate, or be persistenly raised
Prior HCV, cleared infection
Negative: becomes positive in 6-24 weeks
Detectable within 1-2 weeks, usually very high
May be up to 7 to 10 times above the normal level
Acute HCV infection
May be persistently normal, persistently raised or fluctuate
Chronic HCV infection
There are at least six different strains of hepatitis C, known as genotypes. They are numbered from 1-6, in the order that they were discovered.
Each genotype has variations, called subtypes. Subtypes are named by lower-case letter (ie a, b, c, etc). One genotype cannot change into another, but it is possible to catch more than one genotype at the same time, or to catch a different genotype from the one you already have. You can also catch the same genotype again after successfully clearing the virus with treatment.
It is essential to know your HCV genotype in order to plan when to use treatment and how long to treat for.
If your clinic hasn't done this, then be more insistent. This is strongly recommended in the guidelines (direct link correct May 2007) from the British HIV Association (BHIVA) for treatment of HIV and hepatitis C coinfection.
Predominant HCV genotype
Europe, North America, Japan
Genotype 1a or 1b
Egypt, the Middle East, Central Africa
Liver enzymes are proteins that have specific functions.
Some of these enzymes leave the liver and enter the blood when the liver is injured.
Several things can cause liver enzyme levels to increase. These include side effects from prescription and over-the-counter medications, herbs, vitamins and supplements, exposure to toxic fumes, high alcohol intake, a new or existing hepatitis infection, and coming off drugs and/or alcohol.
Many HIV drugs can cause liver enzymes to increase -- though not usually to dangerous levels. In some cases, those drugs need to be stopped or switched. People taking HIV drugs (or any other drugs processed by the liver) need to have liver enzyme levels measured with their routine blood tests. This is especially important if they also have hepatitis C (HCV).
Liver enzymes tests are often called liver function tests (LFTs), although they do not really measure liver function. The results from these tests should be looked at in relation to other information.
ALT (alanine aminotransferase ) should be monitored routinely, as if it continues to increase, it may mean HCV is getting worse.
The liver produces ALT, which helps produce salts and amino acids (which are used to make proteins). Increases in ALT are usually a signal of liver inflammation or damage. However, ALT is not a good marker for predicting HCV disease progression, or indicating how much your liver may already be damaged. This is because liver enzyme levels regularly go up and down in people with HCV.
|Normal liver enzyme levels, even over time, do not mean that you have no liver damage.|
Up to a third of people with chronic HCV always have a normal ALT, but some of them will have serious liver damage.
AST (aspartate aminotransferase) is another enzyme involved in the production of amino acids but because it is made in the heart, intestines, and muscles, it is not a sensitive marker for liver injury.
AST is often used to monitor liver inflammation and damage in combination with other tests.
It is important for people with HCV and HIV/HCV to undergo routine monitoring of ALP, GGT, bilirubin, albumin and prothombin time.
Alkaline phosphatase (ALP) is another enzyme that is present in tissues throughout the body, including the liver. If blood levels of ALP increase, this can be a sign of disease or damage to tissues. Your doctor can also test specifically for ALP from the liver. Some medications, including the HIV protease inhibitors atazanavir and indinavir, can cause ALP elevations. Elevated ALP from the liver is a sign of blocked bile ducts caused by liver disease.
Gamma glutamyl transferase (GGT) is enzyme involved in metabolism that is produced in the bile ducts. Any type of liver disease, heavy drinking, and some medications can increase levels of GGT.
Bilirubin is a waste-product from the breakdown of red blood cells. The liver is involved with processing bilirubin. When the liver is damaged, it may be unable to process bilirubin, and the total bilirubin levels increase. Jaundice, dark urine and pale stool are common signals of increased bilirubin. Some drugs, including the HIV protease inhibitors atazanavir and indinavir, can cause increased bilirubin levels.
Albumin is a protein made by the liver. It carries drugs, hormones and waste products through the blood and maintains fluid levels within the body. Abnormally low levels of albumin are a sign of serious liver damage.
PT (prothrombin time; pro-time): PT testing measures the amount of time it takes for blood to clot. When the liver is damaged, its ability to make clotting factors is impaired. If this time increases -- referred to as a prolonged PT interval -- it shows that the liver is not working so well.
People with HCV cirrhosis are at risk for liver cancer. Regular screening can detect early-stage liver cancer.
Usually, screening consists of a liver scan by ultrasound or computed tomography (CT), and a blood test measuring alpha-fetoprotein (AFP; a protein made in foetal liver tissue) levels. Screening is recommended every six months.
You can use this sheet to record your CD4, HIV and hepatitis C viral load, ALT, AST and other test results.
The sheet includes reference ranges for men and women.
These ranges are included as a guide. Different laboratories may use different ranges, and it is important to refer to the reference range that your laboratory is using.
CD4 count: Measured in cells/mm3. Range 0 to over 1600. Higher the better, over 200 reduces risk of opportunistic infections.
HIV viral load: Measured in copies/mL. Range from undetectable to over 1 million (rare).
Hepatitis C viral load (RNA): Measured in IU/mL. Range from undetectable to over 40 million. When over 400,000 it reduces the chance of treatment success.
ALT: Women:7-30 units/L. Men: 10-55 units/L.
AST: Women: 9-25 units/L. Men: 10-40 units/L.
ALP: Women: 30-100 units/L. Men: 45-115 units/L.
GGT: Women: over 45U/L. Men: over 65 U/L.
Bilirubin (direct): 0.0-0.4 mg/dL (US), 0-7 µmol/L (SI units).
Bilirubin (total): 0.0-1.0 mg/dL (US), 0-17 µmol/L (SI units).
Albumin: 3.1-4.3 g/dL (US), 31-43 g/L (SI units).
PT: 11-13.5 seconds (PT 1.5-2 times control is abnormal)
A liver biopsy is where small sample of liver tissue is taken, and examined later under a microscope.
A liver biopsy is considered the best way to assess liver disease. It provides information about both the stage (the amount of scarring) and the grade (amount of inflammation, which drives future scarring) of liver disease. It can also identify other causes of liver disease.
A liver biopsy involves having a needle inserted between the ribs, and into the liver. This then clips and removes a small sample of liver tissue. The procedure can be painful, and carries a small risk of complications (1-3%), such as puncturing other organs or bleeding, and a much, much smaller risk of death (0.1% to 0.01%).
Biopsy is not perfect because there can be errors in sampling and in reviewing. Results may be inaccurate when a sample is too small, or it comes from an area in the liver that is more or less damaged than the rest. Samples also need to be reviewed by a specialist. In addition, the cost of a biopsy may limit how easy this is to access. Despite this it is still the 'gold standard'.
Because a biopsy is not pleasant, many people with HCV are reluctant to take part. Still, many doctors think they offer the best and most reliable way to know the level of liver damage. Luckily, reliance on biopsy as a requirement for hepatitis C (HCV) treatment is an area that is changing.
Some experts think that if you have a high chance of response to treatment (people with genotype 2 or 3, and with lower HCV viral load) you do not need a biopsy before HCV treatment.
A biopsy may be most useful for informing treatment decisions in people with harder-to-treat HCV (genotypes 1 and 4) who may be able to wait for newer therapies if they do not have serious liver damage.
A biopsy should only be performed by an experienced doctor, who has a good record of successful biopsies.
The doctor should guide the needle with an ultrasound scan to reduce the chance of puncturing another organ, and to pinpoint areas of damaged liver tissue for sampling. If you are concerned about the pain, ask your doctor about options for pain management during and after the procedure.
Ask other people about their experiences. It may be easier to find a good doctor by talking with people who have had a biopsy.
There are different systems for measuring liver inflammation and fibrosis. All go from zero to a maximum score; the higher the number the more inflammation or fibrosis.
Ishak: inflammation 0-18, fibrosis 0-6
UK (BHIVA) guidelines define mild liver damage as a modified Ishak score of 3 or less and a fibrosis score of 2 or less, and moderate liver damage has an inflammatory score of 4 or more and/or a fibrosis score of 3 to 5.
However, these scoring systems are not used in every hospital and some clinics prefer to just stage biopsies as mild, moderate or cirrhosis.
Having a biopsy can help you make a treatment decision by showing how damaged your liver is.
Despite the discomfort, and risk of complications, it is an important test for monitoring hepatitis C (HCV) disease over time.
It is therefore recommended during chronic infection, and especially recommended before starting treatment. In untreated, HIV-positive people, a follow-up biopsy is recommended every 2-3 years.
In untreated, HIV-positive people, a follow-up biopsy is recommended every 2-3 years.
UK guidelines say that the risks versus benefits should be weighed for each individual. Many centres feel that the risk of a liver biopsy outweighs the benefit in men with haemophilia.
One doctor said: "I tell people who really don't want a biopsy, that they are important in order to make treatment decisions, and they may need to get one in the future. For example, if someone isn't responding to HCV treatment after 12 weeks, we need to decide whether or not to stop treatment altogether, or to continue with maintenance treatment."
New research is looking at whether results from laboratory tests can be used in place of a biopsy. This could easily change the way that hepatitis C (HCV) is managed in the future.
Studies using combinations of these lab results suggest they are useful for identifying serious liver damage, but it remains controversial whether they are a reliable substitute for a liver biopsy.
Measuring liver stiffness (Fibroscan)
The Fibroscan is a non-invasive approach that is already showing promising results. It is a scan that measures the 'stiffness' or 'elasticity' of the liver, using an ultrasound scan to create waves and measure their speed.
Wave speed is used to determine liver stiffness; the harder the liver tissue, the more rapidly the waves will pass though it.
Although this scan is much less sensitive in detecting mild or moderate liver damage, it is very sensitive at picking up severe damage. It can therefore identify people who need HCV treatment more urgently.
Results are presented as a figure in kilopascals (kPa). The higher the figure, the stiffer and more damaged the liver.
Results from Fbroscan do not equal fibrosis measured on other scores for all patients. However, a score of over 7.2kPa indicates higher likelihood of significant fibrosis (F2 or greater on Metavir and needing HCV treatment) and over 13kPa indicates cirrhosis (F4 on the Metavir scale).
These results need to be interpreted in the clinical context and should be repeated before labelling significant fibrosis/cirrhosis.
Fibroscan is not painful. In the UK, both the Royal Free Hospital and the Chelsea and Westminster Hospital are using Fibroscan to monitor people with HCV/HIV coinfection.
Youtube FibroScan www.youtube.com/watch?v=l_E4ZGmKooA
Youtube liver biopsy www.youtube.com/watch?v=PXTdt_ZtlgM