Important lab markers in HAV infection
Learn about the relationship between ALT, IgG, and IgM levels, and how to interpret a positive test.
Elevated ALT is one sign of hepatitis A infection, but is extremely unspecific. In this video taken from our Viral Hepatitis Lab Essentials course, Dr Wonnerth explains the relationship between ALT, IgG, and IgM levels, how different labs test for them, and whether a positive test indicates an HAV infection in the acute, convalescence, or long-term immunity phase.
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[00:00:00] What blood tests are available in order to diagnose a present or past hepatitis A infection? In order to answer this question, let's take a look at our diagram. The elevated ALT is an indicator of a hepatitis A infection but it is extremely unspecific. We know that there is something wrong with the liver but there are many possible reasons for this. What we need are specific serological markers for HAV. Anti-HAV IgM is the first
[00:00:30] serologic marker to occur. It starts rising early after symptom onset and only drops to undetectable levels, up to six months later, when the infection has cleared. So, when our patient feels they need to go to the doctor, we will already find a positive IgM in the blood. In the course of [00:00:44] infection, IgM is replaced by IgG antibodies. It is important to know that anti-HAV IgG are detectable in the blood for years and confer long-term protection against reinfection. We can also split the course of infection
[00:01:00] into different phases. We can distinguish an acute phase at the beginning, which is characterized by high ALT levels, high IgM levels as well as rising IgG levels. Next, the convalescence phase, with sinking IgM but still rising IgG levels and finally a phase of long-term immunity, when the infection is cleared. When IgM has dropped below the level of detection and IgG stays detectable. The long-term immunity phase actually indicates a past infection but no active infection.
[00:01:30] Taken together, anti-HAV IgM and IgG are the most important lab parameters used to determine what phase of infection our patient is in. So, what happens in the lab? Several systems are available to test for HAV in the laboratory. There are two possible paths to start the diagnostic process, depending on which test system your lab is using. Lab 1 might use a test system, measuring first, anti-HAV IgM antibodies. Lab 2 might start a diagnostic process, by measuring
[00:02:00] IgM and IgG, in one test system. This test is called anti-HAV. When we order hepatitis A testing in lab 1, we first get the results of anti-HAV IgM testing. This is ideal if your clinical question is whether your patient is suffering from an acute hepatitis A infection or not. If the result is positive, then you can confirm that your patient suffers from an acute hepatitis A infection. What happens if the result is negative? First of all, we can exclude an acute infection.
[00:02:30] However, we might want to get a bigger picture so we can add another test called anti-HAV. In this test system, IgM and IgG are detected. Since we already know that IgM is negative in our patient, the result of anti-HAV will shed light on the IgG status of our patient. If the anti-HAV test is positive, our patient has detectable anti-HAV IgG antibodies. That means we're looking at a patient who had either a past infection, that
[00:03:00] has already cleared or our patient has been vaccinated against HAV. In contrast, if the anti-HAV test is negative and thus, IgM and IgG are both negative, our conclusion can only be no infection. Our patient has neither an acute infection nor has he ever been in contact with the virus or the vaccine. When we order hepatitis A testing in lab 2, we first get the results of anti-HAV testing. We have already heard that this test detects IgM and IgG in
[00:03:30] one system. So, if this test is negative, there is no HAV infection. Neither acute nor past. If it is positive, you cannot say whether IgM or IgG are responsible for the positive result. So, our reflex test for IgM has to follow, in order to distinguish an acute infection, with positive IgM from a past infection or immunization, which is characterized by negative IgM and positive IgG. There are also tests that can measure hepatitis
[00:04:00] A antigen or RNA, in stool, very early in the acute phase. These tests are not commonly used, as this is of interest only in rare cases and these tests are only available in specialized laboratories. Now that we know how to interpret lab results in the context of infection phases, we can start working with some real cases.