Hepatitis B: HBsAg VS Anti-HBs

Bottom Line:

HBsAg (Hepatitis B surface antigen) is the one you are most likely to see on routine screening bloodwork for Hep B. If it is positive the person is likely actively infected with Hep B either chronically or acutely.

Memory Aids:

Surface Antigen is the one you want to remember.

Details:

When I first started seeing Hep B screening on bloodwork I was so confused as to whether or not the person was infected or vaccinated or immune or all of those or none of those. It turns out that it’s a bit complicated because several different things could be measured, and when you write the short forms down they all look a bit alike.

Here is some helpful information

When a person is infected with Hepatitis B, they go through various stages which vary in length depending on the particular serotype of the virus they are infected with (there are at least 4) and the characteristics of the person being infected. There are at least 2 phases (possibly more depending on who you talk to) of the disease. The first is “immune-active” where viral DNA and various viral surface antigens will be present in the body. At some point, the person will “seroconvert” to the “inactive-carrier” state where viral DNA and viral surface antigens will no longer be present (they will have been cleared by the immune system), and instead various antibodies to the viral antigens will be detectable.

To make things more complicated, you can divide the immune-active phase into 2 parts: “immune-tolerant” and “immune-clearance”. Many people who live in parts of the world where Hepatitis B is endemic are basically born infected or acquire it very soon after birth. They start out in the immune-tolerant stage where they have high viral loads, but no real symptoms. They can remain in this state for decades, but in order to progress to the inactive-carrier state, they have to pass through the immune-clearance state. This is where they still have high viral loads, but they become symptomatic. The longer they stay in the immune-clearance phase, the sicker they get and some people die of liver failure/cirrhosis at this point. However, many people progress to the inactive-carrier state at which point they are basically immune to future infection. There are some unlucky few who become reinfected again due to reactivation of the virus, but this is rare.

The Hepatitis B vaccine was developed from the Hepatitis B surface antigen. Therefore, people who have been vaccinated will have detectable levels of Hepatitis B surface antibody (i.e. the antibody to the viral antigen), but they may not have other antibodies to viral antigens that may be present in people who obtained immunity through actual infection.

Here are the things most likely to appear on bloodwork related to Hepatitis B.

  • HBsAg (Hepatitis B surface antigen) – This is a protein on the surface of the Hepatitis B virus. If this is detected it indicates active infection (either chronic or acute). It is also the antigen used to produce the Hepatitis B vaccine.
  • HBeAg (Hepatitis B e antigen) – This is a marker of active viral replication. It indicates the person can infect someone else.
  • Anti-HBs (Hepatitis B surface antibody) – This is produced by the immune system after vaccination (with HBsAg) or after seroconversion to the inactive-carrier state in an infected person. It’s presence generally indicates immunity.
  • Anti-HBc (Total Hepatitis B core antibody) – In contrast to anti-HBs, the core antibody is produced at the onset of the infection and remains detectable for life. Therefore, if this is detected it could mean active infection (acute or chronic), or previous infection now cleared. It is not produced when a person is vaccinated, therefore it can be used to distinguish between immune people who have been vaccinated or not. I believe this includes both the IgM and IgG fractions.
  • IgM anti-HBc (IgM antibody to Hepatitis B core antigen) – This antibody appears just after infection and then disappears within weeks. I believe this is the only the IgM fraction of the Anti-HBc measurement above.

References:

Here is a fantastic summary from the CDC (it turns out they have an entire Viral Hepatitis Division!)

Medscape has a great section on Hepatitis B workup

Wikipedia’s page is also excellent

This paper is a great summary of the Hepatitis B disease process and seroconversion: Liaw Y-F. HBeAg seroconversion as an important end point in the treatment of chronic hepatitis B. Hepatology International. 2009;3(3):425-433. doi:10.1007/s12072-009-9140-3.

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