Help me understand, please. How is it that someone can be born with HBV and not clear it? How is it that adults can be acutely infected and not clear it? How is that not all people can clear the infection? Why the chronic pathologic response, without normal seroconversion? How is that in chronic infections, vaccination is not beneficial?
I’ll answer your questions in the order you asked them.
- Most people are not born with HBV but are infected at or shortly after birth.
- An infant/small child’s immune system is immature and does not work as well as an adult’s, so HBV can more easily become fully established in the liver in the absence of a robust immune response. The virus also actively interferes with the immune system by a number of different manners, some but not all of which are known. That prevents an effective immune response from developing as the person gets older.
- The chronic, pathological response is primarily due to a partially effective immune response. It is strong enough to keep the virus from overwhelming the liver (ie, fulminant hepatitis), but not strong enough to get rid of HBV. In the process, your white blood cells cause inflammation in the liver and kill a fraction of the infected liver cells. Over time, that damage adds up, leading to HBV-induced pathology.
- Chronically infected patients rarely seroconvert (to HBsAg) because the virus interferes with this process. We don’t know most of the mechanisms in detail, but part of it is that infected cells produce massive amounts of HBsAg, and a safety circuit in the immune system causes it to turn itself down when a target protein (“antigen”) is at very high levels to prevent over reaction to high levels of antigens (a type of “tolerance” or “anergy”).
- Vaccination does not work in chronically infected individuals because the antigen in the vaccine is just a little bit of HBsAg, and there is already a huge amount of HBsAg in the blood from the infected liver cells that has rendered the immune system unresponsive (tolerant) to HBsAg.
I hope this helps.
John, thank you. That helps quite a bit. Have a great weekend.