Virology/Serology/Immunology
Viruses are some of the most interesting and sophisticated things on the planet! The HIV virus consists of less than 10,000 base pairs of DNA. If you think about all the damage and trouble it has caused our population, it is truly remarkable.
Of the vast amount of viruses in the world, there are only a few which are critical to understand for the clinical laboratory scientist.
Hepatitis B:
Hepatitis B antigens and antibodies are frequently tested on and important to understand. There are two antigens to be aware of, hepatitis B surface antigen, and hepatitis e antigen. There are three antibodies to be aware of, hepatitis B surface antibody, hepatitis B core antibody, and hepatitis B e antibody. Each of these has an abbreviation which can be seen in the table below.
| Name | Abbreviation | Alternative Name |
| Hepatitis B surface antigen | HBsAg | |
| Hepatitis B e antigen | HBeAg | |
| Hepatitis B surface antibody | Anti-HBs | HBsAb |
| Hepatitis B e antibody | Anti-HBe | HBeAb |
| Hepatitis B core antibody (IgM) | Anti-HBc (IgM) | HBcAb (IgM) |
| Hepatitis B core antibody (IgG + IgM) | Anti-HBc | HBcAb |
Watch out for alternative antibody names! They only differ from the name of the antigen by one letter and can cause confusion or mistakes.
You’ll notice there is an IgM and an IgG core antibody. The presence of IgM anti-HBc generally indicates an acute HBV infection. IgM anti-HBc is the first antibody to appear when fighting a HBV infection. The presence of IgG anti-HBc generally indicates a chronic HBV infection. Once infected with HBV, IgG anti-HBc will generally persist for life. Oftentimes total hepatitis B core antibody will be referenced because the two tests commonly run in the clinical lab are total hepatitis B core antibody and IgM anti-HBc. Total hepatitis B core antibody (anti-HBc) simply means IgM and IgG anti-HBc.
With all of these different antigens and antibodies there are a number of different scenarios possible. The presence/absence of individual antigens or antibodies indicate what is going on with the patient. The table below outlines commonly seen scenarios.
| Result | Interpretation |
| HBsAg (-) | Patient is susceptible to HBV |
| Anti-HBs (-) | |
| Anti-HBc (IgG and IgM) (-) | |
| HBsAg (-) | Immunity from a natural infection |
| Anti-HBs (+) | |
| Anti-HBc (IgG and IgM) (+) | |
| HBsAg (-) | Immunity from a hepatitis B vaccination |
| Anti-HBs (+) | |
| Anti-HBc (IgG and IgM) (-) | |
| HBsAg (+) | Acute HBV infection |
| Anti-HBs (-) | |
| Anti-HBc (IgG and IgM) (+) | |
| Anti-HBc (IgM) (+) | |
| HBsAg (+) | Chronic HBV infection |
| Anti-HBs (-) | |
| Anti-HBc IgG (+) | |
| Anti-HBc IgM (-) |
The important thing with HBV is being able to think your way through results. There are cases where results may appear discrepant but let’s start with general rules and the most common cases and then we’ll break down results that are less frequent.
General rules:
1. If a person is negative for HBsAg, they have either not been exposed to the virus or have immunity (natural or from a vaccination).
2. If a person is negative for HBsAg and positive for anti-HBc, the immunity is from a natural infection.
3. If a person is negative for HBsAg and positive for anti-HBs but negative for anti-HBc the immunity is from a vaccination.
4. One type of HBV vaccines are proteins of the HBsAg produced by yeast cells, so building an antibody to the “core” of HBV can only come from natural infection. The vaccine will cause you to build an antibody to HBsAg.
5. In order for a person to have a current infection (acute or chronic) they must be positive for hepatitis B surface antigen (HBsAg).
6. If a person is positive for HBsAg and positive for anti-HBc (IgM) the HBV infection is acute.
7. If a person is positive for HBsAg and negative for anti-HBc (IgM) the HBV infection is chronic.
These rules are just general, and as always there are exceptions to the rules. For example take a look at the results in the table below.
| Result |
| HBsAg (-) |
| Anti-HBs (-) |
| Anti-HBc (+) |
If we followed the above rules we would assume the immunity is from a natural infection, however, in the larger table above, natural immunity will also be anti-HBs (+). So what could be happening here?
There are four possible scenarios:
1. A person who had HBV in the past and resolved the infection may have very low levels or decreasing levels of anti-HBs. HBsAg is negative because the infection was cleared and anti-HBc (most likely IgG) remains for life.
2. The person may have a low level chronic infection and HBsAg levels cannot be detected by the test.
3. The anti-HBc could be a false positive meaning the person is actually susceptible.
4. A person may be recovering from an HBV infection. During the recovery period anti-HBs will not appear for a few weeks after HBsAg has been cleared. It is possible for both HBsAg and anti-HBs to be negative during recovery. Some will refer to this as the window period in acute infection.
HBeAg and anti-HBe:
In acute infections HBeAg appears slightly after HBsAg and disappears shortly before HBsAg in recovering patients. HBeAg can also be present in chronic HBV infections and its presence is indicative of an active infection.
Anti-HBe appear after clearance of HBV and indicate recovery. Anti-HBe can persist and provide immunity for years.
HBV DNA:
HBV DNA is commonly measured using rt-PCR and other methods. It’s another useful tool for elucidating what is happening in a patient. HBV DNA can be detected before HBsAg which can be valuable for blood banking to detect HBV in the blood supply; the HBV DNA viral load can be measured to monitor chronically infected patients or determine how well a patient is responding to therapy; HBV DNA can also be used to detect variants and mutations where serologic tests come back negative.
Other rare cases of HBV:
Due to genetic complexity there are all kinds of HBV types with all sorts of properties. Some HBV can evade the HBV vaccine and are referred to as “escape mutants.” HBV is also known to colonize the liver and be generally undetected by current clinical lab tests. This is referred to as “occult HBV.” If you are interested in learning more, I encourage you to take a deeper dive into the world of HBV because there isn’t a cure yet, more research needs to be done!
HIV:
HIV is screened for using an enzyme immunoassay (EIA) using an antibody to HIV-1 and an antibody to HIV-2. HIV-1 and HIV-2 are the two main types of HIV. They are frequently screened for together, however confirmation is done using a Western blot. Two out of the following three antigens (p24, gp41, or gp120/gp160) must be present to call a test positive.