How Is Hepatitis C Diagnosed?

Hepatitis C viruses are so small that they can only been seen with the most powerful electron microscopes. Yet simple tests can reliably tell whether someone has been exposed to the virus. Other tests can show if someone still has an active infection. Still other tests are able to gauge the extent of damage to the liver.

Often the first sign that something is wrong comes from a standard blood test, which includes a test for enzymes associated with liver function. An abnormal reading alerts doctors to the possibility of liver disease. Several other tests performed by analyzing blood can verify the presence of the hepatitis C virus. One simple test measures signs of antibodies to hepatitis C, small molecules produced by the immune system when it detects a virus. Other tests measure the level of viruses found in the blood and identify precisely which type of hepatitis C is present. The most common tests for hepatitis C include the following:

Enzyme immunoassay

This test detects antibodies to hepatitis C, sometimes called anti-HCV. Antibodies are the tiny molecules the immune system produces when it encounters foreign germs. Even after an infection is over, antibodies often remain in the bloodstream for years. Thus an antibody test can show if someone was exposed to a particular virus, even if the exposure occurred years earlier. The molecules produced to combat hepatitis C have a different shape from antibody molecules produced to thwart hepatitis A, for instance. For that reason, antibody tests are also very specific. They can determine exactly what type of hepatitis a person carries.

The anti-HCV test used today is called EIA-3, because it is the third generation of such tests. It is more specific and sensitive than previously used tests. But it isn't perfect. Sometimes it mistakenly detects antibodies when there aren't any (a false positive reading). Or it can fail to detect antibodies even when someone does have the hepatitis C virus (a false negative). False negatives can occur in people with weakened immune systems that can't produce enough antibodies for detection with EIA. Doctors typically confirm EIA-3 tests using another detection method, such as an RNA test.

HCV RNA

The HCV RNA test looks for the presence of the genetic material that makes up the hepatitis C virus, called RNA. One of two different kinds of methods may be used: polymerase chain reaction (PCR) or transcription mediated amplification (TMA). Unlike an antibody test, which looks for signs that the immune system has responded to hepatitis C, the RNA test looks for the presence of the virus itself. Finding HCV RNA is a reliable way to demonstrate that HCV infection is present.

HCV RNA testing is often used for immunocompromised patients, meaning those whose immune systems may not be able to generate antibodies against the virus. It is also sometimes used for patients exposed to the virus only very recently, whose immune systems may not have had time to generate an antibody response. Doctors also use HCV RNA tests when patients have signs of liver disease but test negative for antibodies.

In patients with a confirmed, active hepatitis C infection, viral load tests can measure the amount of virus found in blood. Viral levels do not necessarily mean a more serious disease or a bad prognosis. But knowing a patient's virus level can help predict how he or she will respond to medication. People with low levels of HCV respond better to alpha interferon and ribavirin, for instance, a combination of drugs often prescribed to treat hepatitis C. Monitoring HCV RNA levels can also provide a measure of how well treatment is working.

Unfortunately, tests that measure viral load are inexact. Different methods used by different laboratories can yield results that are sharply at variance, even when testing material from the same blood sample. What's more, levels of HCV in the blood go up and down on their own by a factor of as much as 10.

Recombinant immunoblot assay

Also called "Western blots," recombinant immunoblot assays are frequently used to confirm HCV antibody tests. For this test, blood is exposed to strips that are treated with proteins from the hepatitis C virus. A change in color indicates that antibodies from the blood have attached to the viral proteins. This shows that the immune system has responded to an infection by generating anti-HCV antibodies. If two or more proteins change color, the test is positive. If only one changes color, the results are considered indeterminate. Doctors may repeat the test, or use another test.

Genotype tests

Another useful test determines the precise form of HCV in the blood. There are six known genotypes, or genetically distinct types, and more than 50 subtypes of hepatitis C. Researchers don't understand all the ways in which these genotypes and subtypes differ. But it is clear that some genotypes respond better to antiviral treatments than others. Patients with genotypes 2 and 3, for example, are two to three times more likely to respond to interferon therapy than patients with genotype 1. Doctors typically prescribe a longer course of treatment, with higher doses of antiviral drugs, to patients infected with genotype 1.

Liver biopsies

By examining tissue taken from the liver, doctors can gauge the severity of damage to the liver. Infection with hepatitis C virus causes several characteristic changes to liver tissue, including inflammation, death of liver cells, and fibrosis (the development of scar tissue).

Doctors typically describe the extent of inflammation and cell death on a scale of none, minimal, mild, moderate, or severe. Fibrosis is typically ranked on a scale of 0 to 4, depending on how widespread it is in the liver.

Liver biopsies are invasive procedures that carry a small but real risk of complications. These include infection, bleeding, and damage to nearby organs. Some patients experience pain that requires medication after undergoing a liver biopsy.

Other tests used to diagnose HCV

Infection with hepatitis C virus can cause a number of telltale changes in levels of enzymes and other factors measured in the blood. These changes are sometimes the first sign that something is wrong. They can also be used to confirm a diagnosis and determine disease progress. Here are some of the biochemical markers that doctors measure:

• Abnormally high levels of the liver enzymes alanine and aspartate aminotransferases.
• The presence of rheumatoid factor, an indication of severe fibrosis or cirrhosis.
• Low platelet and white blood cell counts, an indication of advanced disease.
• Slightly elevated levels of iron and ferritin

Why so many tests?

When doctors suspect hepatitis C infection, several tests are often prescribed to confirm a diagnosis and determine the condition of the liver. The particular tests your physician recommends will depend on what information he or she needs. When doctors suspect a case of acute hepatitis C, for instance -- based on risk factors for the disease along with symptoms such as jaundice, fatigue, and nausea -- they often measure serum alanine transferase. Levels of this enzyme frequently increase tenfold or more in acute hepatitis C.

In as many as four out of 10 patients, anti-HCV is not detected until two to eight weeks after symptoms show up. For this reason, a test for HCV RNA is often performed. Because it detects the genetic material of the virus itself, it is more effective at detecting an early infection than antibody tests. Alternately, doctors may simply wait for a month and do another anti-HCV test.

In 75 to 85 percent of people infected with hepatitis C, the infection becomes chronic, according to the Centers for Disease Control and Prevention. Chronic hepatitis C is diagnosed when the anti-HCV antibody test remains positive and liver enzyme levels remain elevated after six months. To confirm chronic hepatitis C, doctors often use the HCV RNA test to determine if viruses are present in the blood.

References

Testing for HCV Infections: An Update of Guidance for Clinicians and Laboratories. Centers for Disease Control and Prevention

Lauer, G.L., et al. Hepatitis C virus infection. New England Journal of Medicine, The National Institutes of Health Consensus Development Conference management of hepatitis C. Clinical Liver Disease

Chronic Hepatitis C: Disease Management, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Centers for Disease Control and Prevention. Hepatitis C FAQs.