Dr. Pearlman: Viral load is [the number of] viral particles floating in the blood. These are copies of the genetic material of the virus circulating through the body.
Dr. Anania: Viral load is based on technology that lets us measure extremely small quantities of hepatitis C virus RNA, the building block of the virus.
Can I Be Positive for Hepatitis C if I Don’t Have any Measurable Viral Load?
Dr. Pearlman: Being “hepatitis C positive” means you have anti-HCV antibodies in your blood. Having HCV antibodies just means you’ve been exposed to the hepatitis C virus. You can certainly be antibody positive and not have any measurable viral load. One lucky thing this might mean is that you are one of the nearly 20% of people who naturally clear the virus from their bodies. The other possibility is that the virus, during the time blood is drawn, was only temporarily undetectable. HCV viral load in the blood goes up and down, and the test might have caught it on a downswing. So before we tell someone they are negative, we ask them to have the test repeated.
Dr. Anania: After hepatitis C treatment, people still have antibodies to HCV. But if they have no detectable HCV viral load, that indicates recovery from infection — that is, response to treatment and sustained remission. Over a period of time, if a later viral load test comes back undetectable, that patient is in remission.
What Is a High Viral Load and Low Viral Load?
Dr. Pearlman: Anything over 800,000 IU/mL is usually considered high. Anything under that is low viral load … Those with low viral load have a better chance of responding to treatment.
Am I Getting Sicker if My Viral Load Is Rising?
Dr. Anania: Not necessarily. With HCV, viral burden in hepatitis C does not necessarily predict the natural history of clinical disease. And therefore, patients need to understand that we use that measurement to help us guide therapy and response to therapy. We use it in conjunction with other types of laboratory data — liver enzymes, liver biopsies sometimes, and viral genotype. Taken all together, these tests give us a snapshot of what is going on. But viral load numbers themselves do not predict disease.
Dr. Pearlman: Unlike HIV, HCV viral copies do not directly affect a patient’s prognosis and how fast disease is progressing in the liver. Remember, we are measuring blood levels, not what is happening in liver cells. HIV viral load does have a lot to do with quicker progression to AIDS. But HCV viral load does not tell you how fast hepatitis is progressing.
Does a Drop in Viral Load Mean Treatment Is Working?
Dr. Pearlman: We often talk about viral load numbers, but we really look at this in terms of logarithms. A “1 log” change is a 10-fold difference. Significant changes in viral load are a 2-log difference or a 100-fold change. This can be deceptive. If you have a viral load of 800,000 and it drops to 400,000, that seems like a big drop. But it’s only changed by a factor of two. A change from 800,000 to 8,000 would be significant. This is important when we look at response to treatment. Twelve weeks after starting treatment, we see if a person’s viral load has dropped 2 logs or more from baseline. If it has not, we are almost sure the treatment is not going to work.
How Long Must a Viral Load Be Undetectable Before Someone Is “Cured?”
Dr. Anania: Generally we like to see six months of continued undetectable viral load after treatment to say a patient’s virus is in remission. I cannot say they are “cured.”
Dr. Pearlman: After treatment, [patients] have a “sustained virologic response” or SVR. That is defined as undetectable viral load by PCR to under 50 IU/mL for 24 weeks after treatment is completed. If that is the case, that is an SVR. SVR means it’s 98% certain you are cured. But there are very rare cases where people relapse if you check their viral load a year or two out. But it doesn’t mean you can’t get hepatitis C again if you engage in high-risk behaviors.
Does Viral Load Respond Differently to Different Hepatitis C Treatments?
Dr. Pearlman: The two major pegylated interferon products for treating hepatitis C — Pegasys and Peg-Intron in combination with ribavirin — in general show similar response rates. Slight variations may be reported in different clinical trials with different subsets of patients.
What Are the Different Ways of Measuring HCV Viral Load?
Dr. Pearlman: RNA is the genetic material all these tests measure. Most experts measure it by a technique called RNA polymerase chain reaction or PCR. There’s also a technique called branched chain DNA, and a newer technique called transcription mediated amplification or TMA. These are just different ways of measuring HCV RNA. TMA probably gets down to detecting the fewest number of copies, but most labs use PCR.
HCV Viral Load Used to Be Measured in Number of Copies. Now They Use International Units. Why?
Dr. Pearlman: Different laboratories don’t use the same standard for counting copies of HCV RNA. So we’re now moving to an international standard.
Dr. Anania: You can still get a copy number. But using international units (IU) is a way to uniformly report data throughout the world. Many lab tests are reported in this way. It standardizes test results between different labs.”