Viral load testing
 

Rajender Reddy MD: Antibody assays indicate either previous exposure to hepatitis C with recovery or ongoing hepatitis C infection. Antibody assays have false negative and false positive situations, although they are relatively less frequent. HCV-RNA assays are the more specific assays to indicate viral infection.

David Bernstein MD: Viral load testing is the key to determining if someone has hepatitis C or not. There are two main types of viral testing that are used:

Qualitative tests are the most sensitive, specific tests. They report as, "Yes, it's present", "No, it's not present".

Quantitative tests, of which there are numerous types of tests that are in use, give a number. Those numbers may range anywhere from lower limits of detection of 50 international units to those that have higher limits of detection of 850,000 international units or greater than a million international units or even as high as 50 million international units. The sensitivity and specificity of the various HCV-RNA assays used in the evaluation of hepatitis C are 98 to 99%.

In general, HCV-RNA assays are not used for screening. However, there are special circumstances when pooled blood products are put together that blood banks do use the more sensitive PCR testing for screening.

Robert Brown MD: The benefits of using PCR versus antibody or EIA-based testing for blood products is that it eliminates part of the window between infection and the detection of a positive test. For PCR testing, you will be able to detect the virus in the blood within two to four weeks. For the development of

antibody, that takes longer, usually not before 12 weeks and sometimes up to 24 weeks after infection.

qualitative HCV-RNA assays are the most sensitive and most specific tests.

The reason for not using a quantitative test are that quantitative tests have lower limits of detection. And if the amount of virus in the blood falls below the lower limit of detection of the quantitative assay, you will get a falsely negative result while the patient may still have virus in the blood. Therefore, to confirm the positive EIA test, a qualitative HCV-RNA test is what needs to obtained.

Once you have that, it's then indicated in the evaluation of someone who has completed therapy to determine whether or not therapy was successful.

Quantitative assays are very important in the care of patients with hepatitis C who are being considered for therapy. A baseline quantitative HCV-RNA should be obtained prior to initiating therapy. Those levels should be followed during therapy with the hopes that they will go to zero. At the end of therapy, however, a quantitative test is not sufficient to determine ultimate response to therapy; a qualitative test should be obtained.

Results from different quantitative assays can be compared, since the introduction of international units. In the past, we weren't able to do that and that was a major problem when we cared for patients. Now with international units being present and all quantitative assays being reported in international units, you can compare the various quantitative assays, no matter where they were performed.

Rajender Reddy MD: The one concern amongst patients and physicians is that high viral loads are associated with more aggressive liver disease. However, the data would not support this and it has been demonstrated that viral load generally does not correlate with severe liver disease.

There are certain cross-sectional studies that have demonstrated some correlation between the severity of liver disease and the level of HCV-RNA. But most studies would indicate that the correlation between HCV-RNA level and severity of liver disease is rather poor and nonexistent.

How has the availability of newer nucleic acid tests changed the management of hepatitis C?

David Bernstein MD: Newer tests for the evaluation of hepatitis C have become available over the past five to six years. In particular, quantitative assays for the detection of HCV-RNA have become more sensitive to lower levels of virus throughout the blood. What those tests have done has, therefore, enabled us to measure smaller quantities of virus.

The real question is, "how has the detection of smaller quantities of virus changed our practice?" And I would argue that it hasn't. The goal of treatment remains complete eradication of the virus and that's best measured in a qualitative fashion. The lower limits of detection of the quantitative tests have not eliminated the importance of using a qualitative test for determining end response to treatment.

Is there a standard unit of measure for HCV-RNA quantitative assays?

David Bernstein MD: Quantitative HCV-RNA testing used in the United States and around the world is very important. There are many different types of assays that are used; most academic centers have their own assays and various companies have their own assays.

Rajender Reddy MD: This has lead to a lot of confusion in the practicing community because of the variability in the number of copies reported by each of these assays. Therefore, there has been a push to standardize these assays so that they could all be reported in a value that is of practical relevance and comparable between the various assays. And these are now being reported increasingly as international units per mL. And this would allow to compare the various assays in terms of the amount of virus that a patient has at a given time point.

David Bernstein MD: Therefore, a test in hospital A would be comparable to a test in hospital B, because you're looking at international units in a way similar to INR testing is used for following abnormal prothrombin times in patients on Coumadin.