Dear @Mihai_P,
Well actually you are on the right path!
HBsAg is almost entirely (> 99.99%) in the form of subviral particles (SVP) which are very similar to the “good” cholesterol (HDL) in your blood. SVP can get recycled through liver cells (like HDL) but have no HBV genetic material and so cannot support the production of virus. SVP play an important role in the prevention of immune control of HBV replication in chronic infection. Importantly, these particles are produced by a pathway completely distinct from that used to make virus inside infected cells. This is in large part why HBsAg is not affected by currently approved oral antiviral drugs which target viral infection also and why therapy is life long with these medications.
HBsAg is produced from two kinds of infected hepatocytes (liver cells):
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Hepatocytes which contain the active genetic reservoir of the virus (we have a complicated name for this: cccDNA). These cells produce both infectious virus and subviral particles.
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Hepatocytes which contain one or more “broken” copies of the HBV viral genome which has become inserted into the one or more chromosmes. We call this form of HBV genetic material integrated HBV DNA. While these cells are technically “infected”, in its broken form, integrated HBV DNA they contain cannot support the production of virus but can still support the production of SVP. With the progression of chronic HBV infection (to a stage we call HBeAg negative), the shift of production of SVP (and the bulk of HBsAg) occurs mainly to cells with integrated HBV DNA.
We have good data that shows that the level of HBV DNA integration is much higher in cancer cells than in normal cells in the liver. This is because as integration increases over time, more chromosomes, and the genes that they contain, get disrupted by these integration events, leading to cells dividing out of control (cancerous).
HBV DNA integration is a process which begins after the first infection event and progresses over the course of chronic infection. This process of continual HBV DNA integration requires production of new infectious virus and occurs even with low levels of HBV DNA being produced.
Thus while HBsAg is produced from all infected cells in the liver, the level of HBsAg present does not reflect either the number of infected cells nor the proportion of cells with integrated HBV DNA nor how much HBV DNA integration is present is in individual liver cells. HBsAg persistence does indicate an enhanced risk of liver cancer long term but the level of HBsAg present (or even its change over time) does not provide an indication of the risk of developing liver cancer.
Clinicians who understand these features of HBV infection are more likely to understand the importance of early introduction of therapy to suppress viral replication in order to slow down HBV DNA integration as much as possible and lower the long term risk of developing liver cancer as much as possible
Hope this helps.