Hepatitis B Tests Nucleocapsid Proteins

Core, Pre-Core, and "e" Antigen

The picture above shows a liver biopsy from someone with hepatitis B. The liver cells that are infected are making Hepatitis B core protein. Core protein stays in the liver unless the liver cell dies and some of these proteins get into the blood. When the immune system sees these proteins, it can make antibody to core protein (anti-HBc).

Core protein can also be released into the blood if it has an extra bit called the "pre-core" - this longer protein is detectable as the "e antigen" (HBeAg). It should be noted that the "e antigen" does not stand for envelope as it is not found on the surface of the virus. It was noted many years ago that people with e antigen tended to be more infectious than those who did not have e antigen. This is probably because e antigen is made each time the hepatitis B virus grows. The more hepatitis B there is, the more e antigen, the more infectious the person. On the other hand, if there was very little hepatitis B left, you were not very infectious, and e antigen was negative and you can find the immune memory, namely antibody to e antigen (anti-HBe). We now know that this is not always true!

Learning points

• anti-HBc positive: infection with hepatitis B that may be present or resolved. Sometimes, this is the only test that is positive years after infection has resolved.
• HBeAg positive: hepatitis B present at high levels, very infectious. HBeAg is NOT the envelope of the virus.
• anti-HBe positive: hepatitis B resolved or present at low levels, not very infectious.
  • Exceptions: The hepatitis B virus can develop changes or mutations such that it can no longer make the pre-core portion even though there may be a lot of hepatitis B virus around. That is to say, sometimes you can be HBeAg-negative and yet your viral load could be very high. Converseley, you might be HBeAg positive and yet your viral load could be very low. As such, HBeAg and anti-HBe are very poor markers of how infectious you are. So why bother measuring them at all? Well, it turns out that hepatitis B can behave very differently depending on whether you are HBeAg-positive or anti-HBe positive.

It is important to be familiar with all these hepatitis B proteins because all of our tests and many of our new treatments are based on the structure of the virus. If you want to learn more about these specific tests, you can go on to learn about the details about HBsAg/anti-HBs, or HBV DNA or viral load testing.

You can move on to learn about chronic hepatitis B infection or go back to the main page about hepatitis B tests.