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HBsAg vs. HBV DNA (Viral Load)
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HBsAg vs. HBV DNA (Viral Load)

I am trying to get a better grasp on the actual difference between these two components.  I know that the hepatitis B virus has a surface antigen, so measuring the HBsAg quantitatively can give one a good idea of exactly how much of the virus is in the body.  Each virion also contains DNA, which I assume is what is being tested quantitatively when a HBV DNA viral load test is done.  If we have an idea of how much DNA each viron contains, can't we regressively calculate the actual quantity of HBV in our system from this known DNA viral load number?

I'm just wondering because I had a long discussion today with an MD who is working on an HBV research study.  He told me that the HBV DNA viral load test is the "gold standard" and that's the reason the USA uses it.  He also said that you can extrapolate one number from the other with pretty close precision.

Tags: surface antigen, viral load, hbsag, hbv dna
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Avatar_m_tn
I will have a go.
Each HBV virion consists a surface coat of HbsAg and a core enclosing viral hbvdna. When a blood sample is collected and placed inside a test tube, the surface coat is removed (by an enzyme, I think) and the viral hbvdna amount is measured. Therefore, one can talk about number of copies(of virion) or IU/mL of hbvdna. But please remember, we are only measuring the virions released into blood from infected liver cells. There will still be viral dna inside infected liver cells, together with the cccDNA.
However, using cccDNA as a template, a whole lot of HbsAg are also manufactured inside an infected liver cell. Part of the amount is used to coat the new virions as they are released from the cell. But most of the HBsAg are released from the infected liver cells as particles in rod and spherical forms, consisting of only the surface coat of HbsAg with no viral dna. These particles are not infectious (no viral dna). Their number far exceeds that of the infectious virions (by order of thousand folds). So when we measure qHBsAg, we measure HBsAg from these non-infectious particles as well as from the infectious virions.
That is why, we can have "undetectable" hbvdna, but high level of qHBsAg at the same time.
cccDNA is used as a template to produce both HBV dna proteins and HBsAg. However, antivirals inhibit the formation of viral dna package, and therefore the formation of new virions, leading to "undetectable" viral load in the blood. However, antivirals have no effect on the production of HbsAg and their release from the infected cells as non-infectious particles.  Therefore many scientists consider qHBsAg as a surrogate marker of transcriptionally active cccDNA in the infected liver.

As you can see, I am no expert and so the terms used and details are wrong or missing.

What is clear is that both qHBsAg and hbvdna tell us useful information, and the assay for qHbsAg is cheap when compared to assay for hbvdna. Why qHbsAg assay is still not available in the USA and Australia is a mystery.
  
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Avatar_m_tn
I will have a go.
Each HBV virion consists a surface coat of HbsAg and a core enclosing viral hbvdna. When a blood sample is collected and placed inside a test tube, the surface coat is removed (by an enzyme, I think) and the viral hbvdna amount is measured. Therefore, one can talk about number of copies(of virion) or IU/mL of hbvdna. But please remember, we are only measuring the virions released into blood from infected liver cells. There will still be viral dna inside infected liver cells, together with the cccDNA.
However, using cccDNA as a template, a whole lot of HbsAg are also manufactured inside an infected liver cell. Part of the amount is used to coat the new virions as they are released from the cell. But most of the HBsAg are released from the infected liver cells as particles in rod and spherical forms, consisting of only the surface coat of HbsAg with no viral dna. These particles are not infectious (no viral dna). Their number far exceeds that of the infectious virions (by order of thousand folds). So when we measure qHBsAg, we measure HBsAg from these non-infectious particles as well as from the infectious virions.
That is why, we can have "undetectable" hbvdna, but high level of qHBsAg at the same time.
cccDNA is used as a template to produce both HBV dna proteins and HBsAg. However, antivirals inhibit the formation of viral dna package, and therefore the formation of new virions, leading to "undetectable" viral load in the blood. However, antivirals have no effect on the production of HbsAg and their release from the infected cells as non-infectious particles.  Therefore many scientists consider qHBsAg as a surrogate marker of transcriptionally active cccDNA in the infected liver.

As you can see, I am no expert and so the terms used and details are wrong or missing.

What is clear is that both qHBsAg and hbvdna tell us useful information, and the assay for qHbsAg is cheap when compared to assay for hbvdna. Why qHbsAg assay is still not available in the USA and Australia is a mystery.
  
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Avatar_m_tn
Sounds like a good explanation.  

So even though there may be a lot of HBsAg, the Nucleotide/side analogues like ETV and TDF prevent the formation of new virions which have the potential to infect new liver cells?  Less infected liver cells = less immunosuppressive response by the body to kill those liver cells = less inflammation and scarring?
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Avatar_m_tn
Scientists believe that the excessive amount of HBsAg in the blood serves to suppress our immune response to HBV infection, as a result, the infected liver cells are not cleared and we have chronic infection.

Antivirals inhibit the formation of new virions, making hbvdna undetectable. However, it is believed small amount of new virions are still being produced, released from the infected liver cells, and will infect/re-infect neigboring liver cells. So in my opinion, antivirals do not lead to less infected liver cells.

Then why do lowering of the amount of new virions by antivirals lead to less inflammation as indicated by normal ALT? The flip side, why do high viral load (high number of new virions) is accompanied by high ALT?

Well, I don't know. I want to know the answer too.
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Avatar_m_tn
this is some how also my understanding but still I came across with some believe that claims that using antivirals will same the immune response (case of interruption of antivirals after 1 year or adding interferon to antivirals) so in this case the immune response is related to HBV DNA and not to qHBsAg.

in the same time a decrease in qHBsAg is a good prediction to sustain response in interferon or in antivirals.

so, maybe the immune response is a combination of qHBSAg and HVB DNA.

just my thoughts.
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Avatar_m_tn
Our immune system is complex. My limited understanding is that our immune cells, such as CD8+ T cells, recognise infected liver cells that are infected by the pieces of hbv viral proteins that are expressed on the surface of infected liver cells. After immune tolerance phase, our immune system should mount attack and kill all the infected liver cells. It doesn't, because these CD8+ T cells are "tired", "exhausted", "depleted". Then why is the immune system active (causing inflammation) when viral load is high, but quiet again when viral load is low?
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Avatar_m_tn

my guess is:
proven: hbsag binds to macrophages and dentric cells
unproven but probable, the binding blocks most of the activation of those immune cells and possibility of these cells to see virions, surface antigen, infected cells so immune response is probably weak and partial

high number of virions can make more response in these cells since hbsag is about the same quantity.it is also found that some immune response even towards hbsag is found on cronic (chronic) carriers on high hbvdna.the bad is as hbvdna lowers even response lowers

antivirals rescue some part of our immune response but making virions so low our immune system has no request to rescue the part of immune response to hbsag, this may explain why stopping antivirals can sometimes lead to hbv clearance

we have to consider another thing, our immune response is not concentrated on virions but on lowering of antigens to produce virions inside the cells and on killing of infected cells, this is why hbvdna is a useless test to measure if our immune response is high or low
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Avatar_m_tn
http://www.ncbi.nlm.nih.gov/pubmed/22422518

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