Early screening for HCV infection

A hepatitis C infection doesn't show up in lab results immediately. It can take up to six weeks before anti-HCV can be detected. So how do you screen a patient who may have used a contaminated needle before antibodies show up in the lab results? In this video from our Hepatitis Labs Essentials course, Dr Wonnerth explains the relationship between anti-HCV and RNA, how to use this to screen for HCV as early as two weeks after infection, and presents a diagnostic algorithm to help you make sense of the results.

Lab investigations are crucial for diagnosing viral hepatic infections, but they can be tricky to interpret. See more cases of viral hepatitis in our course Viral Hepatitis Lab Essentials. Taught by Dr Anna Wonnerth–Certified Family Physician and Laboratory Medicine Specialist at the Hospital of Wiener Neustadt, Austria–you'll be a viral hepatitis expert in no time.

[00:00:00] So, what if my patient's results are not conclusive? There are special clinical and diagnostic situations when lab results have to be repeated again. The first special situation deals with what we call, diagnostic gap. Diagnostic gaps are time periods when we cannot detect important markers of infection, although an infection is present. In hepatitis C, we have the problem of a diagnostic gap early after infection. As we discussed,

[00:00:30] we start our screening by measuring anti-HCV antibodies. However, as you can see, these antibodies are only detectable seven to eight weeks after infection. We call the time period, after infection but before anti-HCV antibodies are produced, the serologic gap. It is important that you keep this in mind. If we test for anti-HCV too early after infection, we may see a negative result, even though infection has occurred. So, how do I avoid the serologic gap?

[00:01:00] For example, what test should I order? If I want to screen a patient, who tells me he used a contaminated needle about six weeks ago, in this case I need to measure RNA levels right away, to avoid the serologic gap. But remember, there is also a molecular gap of two weeks. In this period, we are not able to determine whether an infection has taken place. So, if you believe your patient was recently exposed to HCV, you will have to wait two weeks to detect an early infection.

[00:01:30] In the following weeks, before an immune response begins, it is necessary to measure RNA, to confirm an infection. The second special situation deals with additional testing. In this lesson, I want to focus on the following RNA algorithm. We find a positive anti-HCV screening test but RNA is not detectable. How can we interpret these results? Is this the lab report of a patient with a past infection? With HCV, we first have to exclude two other possibilities, before coming

[00:02:00] to this conclusion. The first possibility, is that the patient suffers from a chronic infection, but RNA levels are temporarily not detectable. Remember, RNA levels fluctuate in chronic courses. So, by definition, this is not a false negative result. It is just a possibility, in the pathophysiological course, of a chronic infection. In order to exclude a possible chronic infection, it is recommended to repeat testing six months later. The second possibility could be a false positive anti-HCV.

[00:02:30] How is that possible? In order to explain this, we should discuss the nature of screening tests. Since we screen healthy and diseased patients, it is important for screening tests to not miss any diseased patients, so we have to set our sensitivity high. Consequently, we will also see positive anti-HCV results in a few healthy patients. Even though they do not have anti-HCV. This is the consequence of choosing high sensitivity over

[00:03:00] specificity. We call this a false positive result. So, how can we find out whether it was a false positive result? We just repeat anti-HCV testing, with the second test system immediately, to confirm or falsify the result. After having repeated both tests and having the results confirmed, so anti-HCV stayed positive and HCV RNA stayed negative, we can rule out a chronic infection and a false positive result. Therefore, there must have been an HCV

[00:03:30] infection in the past, which was cleared. To wrap up, if you see a lab result that suggests a past hepatitis C infection, you must first repeat the test in order to make the right conclusions. Congratulations. Now, you're able to handle the first steps of hepatitis C diagnostics in your everyday routine.