As I see the slides from ARC-520, ARWR said, by reducing HBsAg and immune system can be released for cleaning HBV, and high HBsAg suppresses our immune system. Is there any evidence that immune effect is related to volume of HBsAg?
And by reducing HBsAg volume (not cccDNA voulme, just HBsAg, according to ARC-520 RNAi tech), we can let our immune system be powerful enough to clean the cccDNA?
ARC520 and REP9AC work in similar way by reducing (knock down) the quantity of serum HBsAg. Go to Replicor's website and its HBV page, you will see a simple explanation of the effect of REP9AC, you will also see a list of references to studies that describe the inhibitory effect of serum HBsAg on the immune system.
I browse the website and the diagrams, it seems that the entire academic world all agree that it's HBsAg that inhibit the immune response. Personally, I think it's because we can reduce HBVDNA, we can reduce HBeAg, but we still don't have a way to directly reduce HBsAg yet, so we guess it's HBsAg that stops all our therapies from healing the disease. So everything is too early to say a functinal cure, It's only a way to kill cccDNA directly that can be a 100% guarantee of our cure.
I disagree with your rather unscientific explanation ("we still don't have a way to directly reduces HBsAg, so we GUESS it's HBsAg..."). First of all, we also do not have a way to directly reduce HBeAg, except naturally by ourselves or assisted by Interferon in a portion of patients. Second, REP9AC reduces the serum HBsAg, thus leading to a functional cure together with other immune therapies. Third, the theory here that adding Interferon to an antiviral when qHBSag is very low will lead to a cure. Fourth, why is qHBsAg lowest in the immune inactive(control) phase?
Finally, why do the virus produce so much HBsAg, 1000 to 10000 times more than needed to coat the new virions? What evolutionary advantage does this wasteful production have?
OK, Stephen, thanks for the professional answer. You mentioned virus produce 1000 to 10000 times HBsAg more than needed, I don't quite understand. How do you judge if the volume is more than needed? Does it mean one DNA and one HBeAg just need one HBsAg to build a HBV? So there are redundant HBsAg floating in our blood without being built as a HBV? Or else? Looking forward to your answers.
Stephen, another question I am very interested in:
As we know, we found a way to cure HBV with highest possibility now, it's long-term TDF (reduce HBsAg to a certain level) then combo with Pegintf, at least here in Medhelp we are talking about the therapy very often. But I found it's not a common way for doctors to treat the patient outside Medhelp. Why? Because it's still not offically released? Or because the clinical trial isn't finished yet? Or because our topic is far ahead of common doctors?
I am not a researcher, this is my understanding of what is described in the literature. 1 new virion requires X units of HbsAg + Y units of hbvdna + Z units of HBcAg. Please note, no HBeAg is required. But the infected liver cell, using cccDNA as the template, produces (1,000 to 10,000) x X units of HBsAg for each X units of HBsAg. These (1,000 to 10,000) x X units of HBsAg are formed into many spherical and filament particles consisting of HBsAg only and not hbvdna. These are called SVP (sub viral particles) and released from the infected liver cells into the blood. SVP are not infectious (no dna). So for one 1 new Dane particle, there are many SVP.
This is why, hbvdna may be undetectable but qHBsAg is still measurable in high amount, usually over log 3 iu/ml.
This method is advocated by stef2011 because it is the recommended treatment by researchers in Italy. Stef2011 will be able to give you more details. It is not used by doctors because it has not been written into most guidelines. It is not written in most guidelines because, I guess, there is still no comprehensive data from clinical trials. So we will just have to wait for more results from on-going clinical trials.
Thank you Stephen, guru.
Do you have news of Rep9AC? I noticed it was 3 years ago that some of us starting focusing on this durg, but no updates for a long while. Did it meet the intention of design? Or failed?
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