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High HbsAg count/ low hbvdna
Hey guys I recently got a HbsAg quantitative test done. It showed a value of 22100iu/ml. But my hbvdna is 150iu/ml. Alt 19. Fibroscan 7.5kpa. does this warrant treatment? I'm so scared
I am looking for a lab who can do the hbsag quantitative test. Any suggestions? If you do please indicate the test code
Thanks
Thanks
dont be scared bro, mine is 19,800 They aren't giving me treatment either so u are not alone brother, theres no liver injury apparently so just relax, I know its hard because I too stress too much and it makes things worst, best thing to do is 'stay as stress free as possible, and healthy, You and I will get through this, This is not whats going to kill us brother so dont drive urself crazy. God bless you and your Family
1 Comments
Thank you for your kind words man. It's great to know when you're not alone. I too am confident there will come a day soon when we could F*** this virus for good! I have so much hate for this virus.
Not according to recent studies. Carriers with low viral loads and hbsag levels greater than 1000iu are at 14x increased risk for HCC. Read the sub-heading of inactive carrier in the following article
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4107707/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4107707/
20 Comments
Well, I'm not talking about the need for treatment but about a particular pattern of correlation between hbv dna and hbsag quantities. If you just look at your case; your hbv dna was only 150iu/ml, while your hbsag quantity was 22kiu/ml. Now compare this with mine: hbv dna 2700iu/ml and hbsag quantity 17000. Despite me having many folds more hbv dna than you; my hbsag quantity is a bit lower than yours. That is what I was saying: there is no definite pattern of relationship between hbv dna and hbsag quantities.
And the article that you posted is dealing about how to consider various groups of hepB patients for treatment. One important new info I got from it is that hbsag quantity should play a greater role in the decision for treatment. And I fall in that particular group of patients who are considered to be 'inactive' carriers becasue their hbv dna is lower than 20k, have persistent normal lft, and no liver inflammation or injury. But if someone is hbeag- and with hbsag quantity that exceeds 1000iu, then treatment should be considered even though other indicators are within normal ranges, because these class of patients have a much higher hcc risk/ca. 14 times than those with lower hbsag than 1k.
Thanks for the link.
And the article that you posted is dealing about how to consider various groups of hepB patients for treatment. One important new info I got from it is that hbsag quantity should play a greater role in the decision for treatment. And I fall in that particular group of patients who are considered to be 'inactive' carriers becasue their hbv dna is lower than 20k, have persistent normal lft, and no liver inflammation or injury. But if someone is hbeag- and with hbsag quantity that exceeds 1000iu, then treatment should be considered even though other indicators are within normal ranges, because these class of patients have a much higher hcc risk/ca. 14 times than those with lower hbsag than 1k.
Thanks for the link.
Yes, you've been right about no correlation between levels of HBsAG and HBV DNA in HBeAg negative patients. The reason why guys like us are at an increased risk is because the bulk of our HbsAg is derived from integrated HBV DNA. Thus a higher HbsAg quantity would show greater frequency of hbv DNA integration, thus induction of more genomic instability and higher risk of cancer.
Your understanding of the correlation of hbsag amount and frequency of integration and resulting risk of precancerous hepatocyte clones is quite correct. Unfortunately antiviral replication inhibition treatment will not lead to a major effect against the integrated cells.
What is needed is a treatment that reduces those clones with integrated hbsag gene segments.
What is needed is a treatment that reduces those clones with integrated hbsag gene segments.
Atleast the antiviral therapy would reduce or potentially halt further integration of HBsAG coding sequences in the hepatocyte genome. That could atleast, in theory,delay the hepatocarcinogenisis pathway.
@studyforhope
Do you think my high HbsAg Levels could also be due to recent hbeag seroconversion, and the levels are supposed to decrease hence forth, so not entirely a marker for frequency of integration. Im 24 btw
Do you think my high HbsAg Levels could also be due to recent hbeag seroconversion, and the levels are supposed to decrease hence forth, so not entirely a marker for frequency of integration. Im 24 btw
The existing hbsag producing clones contain mostly no more replicating virus genome, so antivirals have no effect there.
If your high hbsag would be the result of a recent HBeAg seroconversion, then your hbv dna levels would also be very high.
If your high hbsag would be the result of a recent HBeAg seroconversion, then your hbv dna levels would also be very high.
But isn't one supposed to enter the inactive stage immediately after HBeAg seroconversion? And expect levels of HBsAG to decline slowly over the years if one remains in this stage?
Studies in the past that have identified true inactive carriers as those with HbsAg levels lower than 1000iu/ml have had a mean age around 40. Considering how most inactive carriers have achieved e antigen seroconversion in their late 20s, it's presumable that all these guys might have had a baseline HbsAg titre much higher than 1000, atleast a log higher, that has reduced Down to below 1000 over a decade? In that case high HbsAg levels at someone my age wouldn't truly reflect the frequency of hbv DNA integration in the genome.
Studies in the past that have identified true inactive carriers as those with HbsAg levels lower than 1000iu/ml have had a mean age around 40. Considering how most inactive carriers have achieved e antigen seroconversion in their late 20s, it's presumable that all these guys might have had a baseline HbsAg titre much higher than 1000, atleast a log higher, that has reduced Down to below 1000 over a decade? In that case high HbsAg levels at someone my age wouldn't truly reflect the frequency of hbv DNA integration in the genome.
You have to ask, where is the hbsag coming from? It is either the cccDNA or the integrated hbsag gene. If it is from cccDNA, then the hbv dna should also be high.
At the HBeAg seroconversion time an effective tcell activity against the core epitopes developed that eliminated a large portion of the cccDNA, clearing many hepatocytes from the cccDNA, but if the cell also had integration of the hbsag gene segment, this will remain.
Elimination of these hbsag only integrated cells is difficult, since only hbsag directed tcell activity is available , which is very weak due to the tolerizing effect of the large amount of hbsag present everywhere.
Presumably, if the integration happens in a cancer sensitive genome position, further mechanisms to eliminate such cells with a cancer potential can be eliminated, independent from the hbsag production by this hepatocyte.
At the HBeAg seroconversion time an effective tcell activity against the core epitopes developed that eliminated a large portion of the cccDNA, clearing many hepatocytes from the cccDNA, but if the cell also had integration of the hbsag gene segment, this will remain.
Elimination of these hbsag only integrated cells is difficult, since only hbsag directed tcell activity is available , which is very weak due to the tolerizing effect of the large amount of hbsag present everywhere.
Presumably, if the integration happens in a cancer sensitive genome position, further mechanisms to eliminate such cells with a cancer potential can be eliminated, independent from the hbsag production by this hepatocyte.
"Can be activated"
Yeah,It would make sense that hepatocytes that have had viral gene fragments inserted into cancer prone locations in their genome would subsequently undergo apoptosis to eliminate the cancer-threat. I would also think such cancer-protective mechanisms are better enforced in younger people than older people. That would explain why most HCC risk models associate no increased HCC risk to guys below 40.
Also, I recently read a paper that identified an enzyme in our body that repairs damaged DNA sequences in our cells. It's no brainer that this enzyme would attempt to 'fix' the genetic damage by eliminating the integrated viral DNA. Also,this would offer an explanation for those patients on nucs who lose s antigen overtime and seroconvert while maintaining normal enzyme levels (absence of an active tcell response).
So in light of all the above menioned points, isn't it rational to assume that even with a high frequency of hbv DNA integration, if one is young (thus exhibits stronger protective mechanisms) and has little transcriptionally active cccdna, that with passage of time the integrated HBV DNA might substantially reduce or potentially eliminate, as is the case with surface antigen seroconverters on NUCs, and that not all is lost and you can still modulate your risk for HCC?
Also, I recently read a paper that identified an enzyme in our body that repairs damaged DNA sequences in our cells. It's no brainer that this enzyme would attempt to 'fix' the genetic damage by eliminating the integrated viral DNA. Also,this would offer an explanation for those patients on nucs who lose s antigen overtime and seroconvert while maintaining normal enzyme levels (absence of an active tcell response).
So in light of all the above menioned points, isn't it rational to assume that even with a high frequency of hbv DNA integration, if one is young (thus exhibits stronger protective mechanisms) and has little transcriptionally active cccdna, that with passage of time the integrated HBV DNA might substantially reduce or potentially eliminate, as is the case with surface antigen seroconverters on NUCs, and that not all is lost and you can still modulate your risk for HCC?
Here's the link to the study
https://www.eurekalert.org/pub_releases/2017-09/uoz-hlc091117.php
https://www.eurekalert.org/pub_releases/2017-09/uoz-hlc091117.php
Unfortunately, this caspase mechanism of repair does not apply to integrated sequences. They are seen as chemically normal DNA and the only way to eliminate them is by killing the affected cell.
The integration into an oncogenic genomic site is only the first step in a stepwise progression to the full cancer phenotype. Therefore it will take many years to reach the stage of actual liver cancer.
The vast majority of integrations are not in an oncogenic site, but this does not matter, since in the end each cancer originates from a single fully transformed cell.
Preventing further chronic inflammatory stress in the liver however will slow the stepwise progression.
NAPs have the potential to selectively induce at least preapoptosis in cells synthesizing the surface antigen, since they block the assembly of the monomers from the ER membrane into the spherical hbsag particle. This will lead to accumulation of monomers in the ER membrane, to which the cell can react with apoptosis. in this way NAPs have the fascinating chance to selectively eliminate hbsag producing cells without the requirement of much Tcell participation. Thats why the hbsag remains extremely low even after the blocking effect of the treatment is long gone. If those cells would not have died, a quick rebound of hbsag would occur. The combined use of an apoptosis enhancer that speeds killing of preapoptotic cells, like birinapant, will dramatically enhance this effect.
The vast majority of integrations are not in an oncogenic site, but this does not matter, since in the end each cancer originates from a single fully transformed cell.
Preventing further chronic inflammatory stress in the liver however will slow the stepwise progression.
NAPs have the potential to selectively induce at least preapoptosis in cells synthesizing the surface antigen, since they block the assembly of the monomers from the ER membrane into the spherical hbsag particle. This will lead to accumulation of monomers in the ER membrane, to which the cell can react with apoptosis. in this way NAPs have the fascinating chance to selectively eliminate hbsag producing cells without the requirement of much Tcell participation. Thats why the hbsag remains extremely low even after the blocking effect of the treatment is long gone. If those cells would not have died, a quick rebound of hbsag would occur. The combined use of an apoptosis enhancer that speeds killing of preapoptotic cells, like birinapant, will dramatically enhance this effect.
Wow! If that is really how NAPs established functional Control, then there should be a dramatic decline in the risk for liver cancer. I guess it would place us in the same risk zone as those with low viremia and HbsAg levels following the natural history of HBV.
But what I don't understand is if NAPs really force HbsAg encoding host cells to undergo apoptosis, why is an Alt flare absent until IFN is administered, which would suggest elimination of such cells by tcell mediated killing and not apoptic mediated mechanism, unless IFN has a direct effect on stimulating the latter action too.
But what I don't understand is if NAPs really force HbsAg encoding host cells to undergo apoptosis, why is an Alt flare absent until IFN is administered, which would suggest elimination of such cells by tcell mediated killing and not apoptic mediated mechanism, unless IFN has a direct effect on stimulating the latter action too.
The naps will sensitize the cells that produce hbsag for apoptosis or necroptosis, but the additional proapoptotic signal provided by interferon, gamma interferon or TNFalpha, which are produced by class II helper Tcells will drive the process to completion. Birinapant will further enhance this mechanism in cases where ifn or thymosin alpha is not sufficient .
In the latest trial it can be seen that the flares induced by ifn only are much weaker than when naps are present at the same time, pointing again at the sensitizing role.
A tcell activation or direct ifn action has little chance to eliminate the integrated only cells, unless it would be strongly targeted at the class I hbsag specific MHC presented epitopes at the hepatocyte surface. This is a major reason why ifn therapy is so ineffective in achieving hbsag seroconversion.
In the latest trial it can be seen that the flares induced by ifn only are much weaker than when naps are present at the same time, pointing again at the sensitizing role.
A tcell activation or direct ifn action has little chance to eliminate the integrated only cells, unless it would be strongly targeted at the class I hbsag specific MHC presented epitopes at the hepatocyte surface. This is a major reason why ifn therapy is so ineffective in achieving hbsag seroconversion.
Thanks for your invaluable insight. This would mean that these drugs from replicor would form the true backbone in future combination therapies aimed at achieving a cure. I feel like all the immonomodualting drugs that have been tried in the past and have failed would have had a real chance at demonstrating their true prowess in combination with a drug like that by replicor.
How long do you think would it take for such a curative treatment to come out? Keeping in mind all the progress that is being in hepatitis B research and the various promising drugs that are in clinical development?
How long do you think would it take for such a curative treatment to come out? Keeping in mind all the progress that is being in hepatitis B research and the various promising drugs that are in clinical development?
Combination treatment with two experimental therapies is currently not allowed by the fda or European drug authorities.
Replicors developmental path is slow since it needs combination for proper duration with at least interferon and an antiviral and then a long follow up to show that the hbsag seroconversion are truly stable.
The need for weekly infusions makes it hard to sell this therapeutic approach to a company like eg Gilead , since the practical procedure to treat patients post approval is difficult and expensive to establish and maintain.
It is so much easier to just make and sell a package of pills.
The "idea" to switch from IV to subcutaneous administration sounds nice, but the relatively large amount of drug that needs to be applied weekly makes it not feasable, since very strong local reactions to naps upon sc administration are a fact.
Replicors developmental path is slow since it needs combination for proper duration with at least interferon and an antiviral and then a long follow up to show that the hbsag seroconversion are truly stable.
The need for weekly infusions makes it hard to sell this therapeutic approach to a company like eg Gilead , since the practical procedure to treat patients post approval is difficult and expensive to establish and maintain.
It is so much easier to just make and sell a package of pills.
The "idea" to switch from IV to subcutaneous administration sounds nice, but the relatively large amount of drug that needs to be applied weekly makes it not feasable, since very strong local reactions to naps upon sc administration are a fact.
I believe replicor owners are as much dedicated to expediting the advancement and approval of their drugs as Gilead shall be if it purchased replicor. Replicor drugs have been progressing through the clinical process without much delay between trials, and hopefully this shall remain the case if results continue to remain positive.
Rep drug treatment isn't intended to be long term, instead it will follow the same finite course as interferon injections. If interferons like zadaxin, Pegasys and lambda havent taken longer than average to reach the market, I doubt things will be any different for rep2139.
Btw you continue to mention use of birinapant as a potential anti hbv therapy, even though it failed phase 1 trials, and likely has no chance for future development?
Are you sure FDA doesn't allow combo studies of different experimental drugs? Because I read articles of collaborations between springbank and Arbutus to try combining their experimental drugs to see if a pronounced anti hbv activity could be achieved. Also how J&J recently backed out of a collaboration with different pharma companies that were collectively working on a experimental combination therapy for HCV.
Rep drug treatment isn't intended to be long term, instead it will follow the same finite course as interferon injections. If interferons like zadaxin, Pegasys and lambda havent taken longer than average to reach the market, I doubt things will be any different for rep2139.
Btw you continue to mention use of birinapant as a potential anti hbv therapy, even though it failed phase 1 trials, and likely has no chance for future development?
Are you sure FDA doesn't allow combo studies of different experimental drugs? Because I read articles of collaborations between springbank and Arbutus to try combining their experimental drugs to see if a pronounced anti hbv activity could be achieved. Also how J&J recently backed out of a collaboration with different pharma companies that were collectively working on a experimental combination therapy for HCV.
I believe replicor is financed by a venture capital group. If this is sufficient to fund even an expensive phase 3 trial is hard to say.
They also have to first determine which nap to finally use. 2139 was an unhappy choice after the 2055 showed too many inflammatory side effects due to non methylated Cs in the sequence. But 2139 was also designed to have very slow elimination characteristics due to the methoxy group added to the ribose ring at every nucleotide. The hope was to prolong infusion intervals, use a much lower dose due to accumulation and to reduce the cpg effect by systematic c methylation. And indeed the drug accumulates to high levels, but a strange unforseeable problematic effect became soon apparant. The naps only work in transit towards a final storage compartment in the hepatocyte, most likely stably chelated to abundant calcium in the ER lumen. Thus 2139 needed an even higher dose of 500mg compared to 400mg of the 2055 and it accumulates to problematic levels with no further activity despite its presence in the liver. It also costs twice as much as 2055. Therefore now as a fix to the problematic overstability 2165 was introduced, which has breakage points engineered inside the 2139 sequence to allow catabolic enzymatic degradation.
The decision to use only 2165 for future trials will probably be made after the results of the recent comparative trial are fully available.
it is hard to say if this will lead to a delay by questioning of the previous 2139 results as a basis for continuation with 2165.
I am not really sure how difficult a dual experimental drug trial would be in terms of approval. But at any rate successful cooperation between different Pharma companies seems to be rather rare.
They also have to first determine which nap to finally use. 2139 was an unhappy choice after the 2055 showed too many inflammatory side effects due to non methylated Cs in the sequence. But 2139 was also designed to have very slow elimination characteristics due to the methoxy group added to the ribose ring at every nucleotide. The hope was to prolong infusion intervals, use a much lower dose due to accumulation and to reduce the cpg effect by systematic c methylation. And indeed the drug accumulates to high levels, but a strange unforseeable problematic effect became soon apparant. The naps only work in transit towards a final storage compartment in the hepatocyte, most likely stably chelated to abundant calcium in the ER lumen. Thus 2139 needed an even higher dose of 500mg compared to 400mg of the 2055 and it accumulates to problematic levels with no further activity despite its presence in the liver. It also costs twice as much as 2055. Therefore now as a fix to the problematic overstability 2165 was introduced, which has breakage points engineered inside the 2139 sequence to allow catabolic enzymatic degradation.
The decision to use only 2165 for future trials will probably be made after the results of the recent comparative trial are fully available.
it is hard to say if this will lead to a delay by questioning of the previous 2139 results as a basis for continuation with 2165.
I am not really sure how difficult a dual experimental drug trial would be in terms of approval. But at any rate successful cooperation between different Pharma companies seems to be rather rare.
Re birinapant. It was originally in development by tetralogic as a treatment for several cancers, mostly in combo.
The trial with hbv patients already on antivirals and with undetectable DNA was done in Australia and was terminated after a few weeks, because some patients developed Bells palsy, just like in the cancer trials and this was considered a stopping signal for the trial.
No partial results were ever revealed. Lack of success in the cancer trials forced tetralogic to sell all technology to Medivir.
But some doctors continued to investigate the potential of birinapant in a private setting. Due to the inability to induce apoptosis in cells not already having a stress signal, like the ones with hbsag only integration, a strong effect on the hbsag formation is not expected and was not observed in birinapant solo treatment phases. But in combination with naps a truly dramatic enhancement of hbsantibody was observed, reflecting the killing of the hbsag integrated hepatocytes presensitized by naps treatment. On off treatment phases confirmed the effect to exist only when both naps and birinapant were simultaneously given. This was in patients responding to naps plus immunomodulation alone with only small antibody titers.
it might never see further development, but this was the closest to a functional cure I have ever seen.
One needs to understand that birinapant will only induce apoptosis in cells already responding with early apoptosis mechanisms to some internal or external stress signal, like the TNFalpha produced by helper Tcells in the close vicinity of fully infected hepatocytes, but not in integrated cells, unless the naps induced accumulation of hbsag monomers starts a stress response.
The trial with hbv patients already on antivirals and with undetectable DNA was done in Australia and was terminated after a few weeks, because some patients developed Bells palsy, just like in the cancer trials and this was considered a stopping signal for the trial.
No partial results were ever revealed. Lack of success in the cancer trials forced tetralogic to sell all technology to Medivir.
But some doctors continued to investigate the potential of birinapant in a private setting. Due to the inability to induce apoptosis in cells not already having a stress signal, like the ones with hbsag only integration, a strong effect on the hbsag formation is not expected and was not observed in birinapant solo treatment phases. But in combination with naps a truly dramatic enhancement of hbsantibody was observed, reflecting the killing of the hbsag integrated hepatocytes presensitized by naps treatment. On off treatment phases confirmed the effect to exist only when both naps and birinapant were simultaneously given. This was in patients responding to naps plus immunomodulation alone with only small antibody titers.
it might never see further development, but this was the closest to a functional cure I have ever seen.
One needs to understand that birinapant will only induce apoptosis in cells already responding with early apoptosis mechanisms to some internal or external stress signal, like the TNFalpha produced by helper Tcells in the close vicinity of fully infected hepatocytes, but not in integrated cells, unless the naps induced accumulation of hbsag monomers starts a stress response.
I've read that there is no any meaningful relationship between hbv dna quantity and hbsag quantity, it is just random. My hbv dna was 2700IU/ml and hbsag quantity, 17000IU/ml a few weeks ago.
I wonder why could it be so high when hbvdna is so low. It's not usual according to all the research I have done
4 Comments
My doc says that treatment won't be given if viral load (DNA) is as low as yours.
Do you pay for your own medicines or are they covered under a program/insurance?
I am an Indian living in US. I have to pay for it, I am assuming.. though I haven't been advised for medicines.
What did you finally decide? Are you going to take medication?
What did you finally decide? Are you going to take medication?
I was advised to start medications since a high HbsAg titre is associated with an increased risk with HCC. Hopefully, the treatment will bring down HbsAg levels with time.
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