Aa
Response to peg 2b + tdf + vit d
Hbsag baseline 6480
After 12 weeks tdf+peg 2b+sim+ntz+artesunate+herbs+vit d
Hbsag 10500
Today's hbsag 8543 after 16 weeks and stopping of all supplements continuing tdf peg and vit d (178ng/ml)
Is the drop related to peg and supplement stoppage or just simple natural fluctuation?
Will continue peg 2b for next 4weeks.
After 12 weeks tdf+peg 2b+sim+ntz+artesunate+herbs+vit d
Hbsag 10500
Today's hbsag 8543 after 16 weeks and stopping of all supplements continuing tdf peg and vit d (178ng/ml)
Is the drop related to peg and supplement stoppage or just simple natural fluctuation?
Will continue peg 2b for next 4weeks.
feeling is a bit harsh and unpleasing till first 2 months, gradually it'll decrease in intensity but throughout there will problems like nausea, vomiting, low grade fever, anorexia, weight loss. i too took vit d but not sure what next besides peg and tdf helps.
How did the treatment make you feel? What helped besides the vitamin d. I'm so nervous taking tdf and pegs or just peg mono. I'm 26
...if delayed response then you could expect it to decrease even more as the time passes...
If you did all measurement at the same lab then it could be a delayed pegasys effect.
If you used different labs it could be a variation between different lab testing machines/materials.
Hard to know for sure...
If you used different labs it could be a variation between different lab testing machines/materials.
Hard to know for sure...
today approx after one year of tdf treatment and 6 months ifn meanwhile(stopped), my hbsag has returned back to low levels, lower than baseline(6480iu) ie.4169iu/ml. This is the lowest level of hbsag i met till now. I am on tdf and herbal caps. WHAT DOES THIS LOWERING SIGNIFIES? Is it just a simple fluctuation in immunity or drug induced? What shall be the future expectations?
Sorry for you .maybe next time you will clear.i don't know why with such lucky patients works and with others no?!
Sorry it didn't work for you but I give you much credit for trying. Best wishes for better in the future!
yeah steff right said.. i just gave it a push thinking i might create an odd but no it is'nt that easy. Will continue tdf and retry ifn only in combo if something promising comes in future. Thanx for giving again "the hope"!
i dont think it is realistic at all to think about hbsag loss in less than 10 years of continuous therapy
only those with low hbsag baseline have good chances, with 6000iu baseline we already knew chances were almost null
only those with low hbsag baseline have good chances, with 6000iu baseline we already knew chances were almost null
pegintf failure is very very common, after more than 5 years on tdf or etv there is cd8 cells partial recovery and then pegintf will respond (i mean it will be able to lower hbsag) for now just check hbsag every year on tdf, it will decline back to baseline and probably even less than 6000iu/ml but it is a slow process, it never works by few years
i started end 2009 and now at 6 years hbsag looks as planned less than 1000iu/ml, i just expect hbsag loss at 10-15years unless i run pegintf again
i started end 2009 and now at 6 years hbsag looks as planned less than 1000iu/ml, i just expect hbsag loss at 10-15years unless i run pegintf again
with an unhappy ending i ve decided to stop peg ifn further. Results hbsag have furthr increased at 24 weeks 12070iu. I started at 6400iu ended double after 6 months. sad end! Still proceed my life with hope of success someday somehow coz thats the way one can live..Hope! Hbv is really unpredictable.
I had a quick look at the rise of qHBsAg at the start of Interferon treatment when it was first mentioned by stef2011 and you offered the possible explanation of a burst of release of intracellular HBsAg from destroyed infected cells. But I don't notice any concurrent rise in ALT that usually occurs with these cell deaths.
I agree that analysts' comments are not that important, but the fact that it was raised by one as saying the integration explanation is not convincing and the markets' tepid reactions may say something. Hopefully, attendees at the AASLD 2015 meeting will give their reactions. As Lorcanini said, if the high level of integration is true in human, it will put into doubt many of the new treatment approaches.
I think that someone from Arbutus pointed out the same advantage of RNAi over NAP with regard to ER stress.
I wish RNAi experts will use the X and E genes' triggers to study their specific effects on HBV. Arrowhead now seems to wake up to the fact that reducing HBeAg, using RNAi, may lead to e-seroconversion. Silencing of the X-gene should also have some interesting effects.
I agree that analysts' comments are not that important, but the fact that it was raised by one as saying the integration explanation is not convincing and the markets' tepid reactions may say something. Hopefully, attendees at the AASLD 2015 meeting will give their reactions. As Lorcanini said, if the high level of integration is true in human, it will put into doubt many of the new treatment approaches.
I think that someone from Arbutus pointed out the same advantage of RNAi over NAP with regard to ER stress.
I wish RNAi experts will use the X and E genes' triggers to study their specific effects on HBV. Arrowhead now seems to wake up to the fact that reducing HBeAg, using RNAi, may lead to e-seroconversion. Silencing of the X-gene should also have some interesting effects.
there are likely two independent mechanisms at play, as explanations of post ifn hbsag rises.
One , in the early phase of ifn treatment, is an initial burst in cell lysis that might wash out a lot of intracellular preformed surface antigen, leading to the temporary increase. We have seen similar effects in tight analysis around ALT flares.
the second mechanism, more sinister, is the one I have described above.It might well depend on the subtype of hepatocyte carrying the integration aka known as clone, and its responsiveness to regeneration signals that arise as a result of cell killings.
Regarding the expanded DNa inegration as a cause for arrowheads failure to lead to sufficient hbsag suppression in e neg patients, it is actually not serving the companys product value very much.
Locarnini and Gish seem to like or might even have provided that new paradigm. I am not guided by them, but find the explanation quite intriguing, as unpleasant as it might be.
Stock analysts opinions regarding detailed phenomenons in cellular pathology are not useful to tilt the scale of insights either way.
Now that we can seemingly explain the differential failure of arc 520, owing to the iRNA target sequence location around the surface antigen gene, we might look forward to a truly improved version 521, that will place the targets smartly enough to hack down also the messages from integrated surface antigen genes.
Of note, the replicor inhibition of hbsag particle release applies to integrated just as effective as to cccDNa produced hbsag.
However, thre is a slight but possible important advantage of the arc 521 on the horizon, that i would like to mention. While the magnitude of the effect even for 521 seems to be still below the power of the naps, the arc destroys the messenger RNA, leading to a non formation of the surface antigen component monomer protein, as it is normally formed at the ER membrane,
and later, aside from being a precursor to the subviral particle formation, also spills out in substantial amounts to the external cellular membrane.
At the liver cell membrane it will absorb anti hbs antibodies in substantial likely large amounts, participating substantially to the depletion of the antibody from the circulation and even more so, from the liver extracellular space, eliminating any chance for the antibody to do what it is primarily meant to do: Bind and neutralize newly budding and forming virions or DAne particles, stopping or reducing the endless cycle of internal reinfection.
The replicor blockage will only block the formation of the subviral particles, but will not remove the cell surface hbsag monomers capable of binding the antibody. The arc 521 should be able to do just that, helping to recover /release antibody concentrations intrahepatically to effective entry inhibitory levels, if the overall efficiency is high enough, which remains to be seen.
One , in the early phase of ifn treatment, is an initial burst in cell lysis that might wash out a lot of intracellular preformed surface antigen, leading to the temporary increase. We have seen similar effects in tight analysis around ALT flares.
the second mechanism, more sinister, is the one I have described above.It might well depend on the subtype of hepatocyte carrying the integration aka known as clone, and its responsiveness to regeneration signals that arise as a result of cell killings.
Regarding the expanded DNa inegration as a cause for arrowheads failure to lead to sufficient hbsag suppression in e neg patients, it is actually not serving the companys product value very much.
Locarnini and Gish seem to like or might even have provided that new paradigm. I am not guided by them, but find the explanation quite intriguing, as unpleasant as it might be.
Stock analysts opinions regarding detailed phenomenons in cellular pathology are not useful to tilt the scale of insights either way.
Now that we can seemingly explain the differential failure of arc 520, owing to the iRNA target sequence location around the surface antigen gene, we might look forward to a truly improved version 521, that will place the targets smartly enough to hack down also the messages from integrated surface antigen genes.
Of note, the replicor inhibition of hbsag particle release applies to integrated just as effective as to cccDNa produced hbsag.
However, thre is a slight but possible important advantage of the arc 521 on the horizon, that i would like to mention. While the magnitude of the effect even for 521 seems to be still below the power of the naps, the arc destroys the messenger RNA, leading to a non formation of the surface antigen component monomer protein, as it is normally formed at the ER membrane,
and later, aside from being a precursor to the subviral particle formation, also spills out in substantial amounts to the external cellular membrane.
At the liver cell membrane it will absorb anti hbs antibodies in substantial likely large amounts, participating substantially to the depletion of the antibody from the circulation and even more so, from the liver extracellular space, eliminating any chance for the antibody to do what it is primarily meant to do: Bind and neutralize newly budding and forming virions or DAne particles, stopping or reducing the endless cycle of internal reinfection.
The replicor blockage will only block the formation of the subviral particles, but will not remove the cell surface hbsag monomers capable of binding the antibody. The arc 521 should be able to do just that, helping to recover /release antibody concentrations intrahepatically to effective entry inhibitory levels, if the overall efficiency is high enough, which remains to be seen.
I am still not convinced that the results of ARC520 study in chimps indicating a high degree of integrated HBV s-gene can automatically apply to human HBV. One stock analyst described this explanation offered by ARC520 about its poor result with HBeAg negative patients as a farce and an excuse.
The increase in HBsAg in Interferon treatment usually occurred at the beginning of treatment which does not seem to gel with an increase in s-gene integration.
The increase in HBsAg in Interferon treatment usually occurred at the beginning of treatment which does not seem to gel with an increase in s-gene integration.
The secret to this paradoxical increase in hbsag on ifn therapy might well be the presence of a high percentage of surface antigen fragment only chromosomal integration.
These cells are hardly recognizable by immune mechanisms and basically behave like normal hepatocytes that simply produce one additional protein from a chromosomal gene. They can divide normally and will partizipate in the replacements of dying liver cells that are fully infected.
Thus replacement of ifn activated immune elimination will paradoxically in higher numbers of these fragment only integrated surface antigen producing cells.
The latest results from the arrowhead trials have indeed provided strong and somehow painful evidence that fragment integrated surface antigen production amounts to an astounding high percentage of the total surface antigen level.Their interfering RNA drug segments do not block these integrated hbsag gene segments , because the interference targets inside a promoter area in front of the actual coding sequence, that is not integrated in the intra hepatic gene transfer and therefore is not blocked by the drug.
Because of this, infections before the time of high frequency integrations were very responsive to the drug, with more than 90% hbsag reductions at the highest dose, while the long standing e negative patients responded with a reduction of only 60%, basically quite useless, because apparantly 40% of the surface antigen is synthesized from untouchable integrated gene fragments.
The cells with these fragments will divide, partizipate in the regeneration of iimmune eliminated liver cells and henceforth produce even more surface antigen.
These cells are hardly recognizable by immune mechanisms and basically behave like normal hepatocytes that simply produce one additional protein from a chromosomal gene. They can divide normally and will partizipate in the replacements of dying liver cells that are fully infected.
Thus replacement of ifn activated immune elimination will paradoxically in higher numbers of these fragment only integrated surface antigen producing cells.
The latest results from the arrowhead trials have indeed provided strong and somehow painful evidence that fragment integrated surface antigen production amounts to an astounding high percentage of the total surface antigen level.Their interfering RNA drug segments do not block these integrated hbsag gene segments , because the interference targets inside a promoter area in front of the actual coding sequence, that is not integrated in the intra hepatic gene transfer and therefore is not blocked by the drug.
Because of this, infections before the time of high frequency integrations were very responsive to the drug, with more than 90% hbsag reductions at the highest dose, while the long standing e negative patients responded with a reduction of only 60%, basically quite useless, because apparantly 40% of the surface antigen is synthesized from untouchable integrated gene fragments.
The cells with these fragments will divide, partizipate in the regeneration of iimmune eliminated liver cells and henceforth produce even more surface antigen.
if you have no sides and it is fully affordable for you
chances or low but not null, during a study in pisa one patient did not respond at all first year (peg+adv) while second year cleared hbsag and obtained the highest hbsab over 500miu/ml.but chances this will happen are very low to me, what about hbvdna?is there response on it?
chances or low but not null, during a study in pisa one patient did not respond at all first year (peg+adv) while second year cleared hbsag and obtained the highest hbsab over 500miu/ml.but chances this will happen are very low to me, what about hbvdna?is there response on it?
1 Comments
no i do not check dna assuming it to be undectable since m on tdf too for past 9months. 6months back at start of interferon it was 130iu. 9 months bak it was 2400iu.
non response to peg:
hbsag the same
hbsag goes up
hbvdna goes down but no effect on hbsag or no sustained effect on hbvdna
hbsag the same
hbsag goes up
hbvdna goes down but no effect on hbsag or no sustained effect on hbvdna
1 Comments
steff but still hepatologists here like u.s dont rely on hbsag quant. superspecialisation doing few students of gastro here adviced me to continue for 1 year irrespective of hbsag quant. big thing is that most/majority of the doctors still dont trust hbsag q. despite they r in regular touch with latest seminars and cme's.
Why his HBsAg has raised ? I thought that on peginf HBsAg goes down less or more only, but always down.
shall i continue ifn?
no
shall i shift back to peg 2b?
no
surrender and wait for future drugs and till then keep taking tdf?
yes and when hbsag willlower under tdf, let s say by 5years, peg add on can be tried again and there can eb response
no
shall i shift back to peg 2b?
no
surrender and wait for future drugs and till then keep taking tdf?
yes and when hbsag willlower under tdf, let s say by 5years, peg add on can be tried again and there can eb response
Response to peg 2b + tdf + vit d
Hbsag baseline 6480
After 12 weeks tdf+peg 2b+sim+ntz+artesunate+herbs+vit d hbsag 10500
hbsag after 16 weeks and stopping of all supplements continuing tdf peg and vit d (178ng/ml) = 8543 iu
hbsag after 22weeks(3weeks of peg 2a)= 11776iu(highest till now)
so it is clear that m not responding to ifn therapy but some absurd questions in mind?
shall i continue ifn?
shall i shift back to peg 2b?
surrender and wait for future drugs and till then keep taking tdf?
Hbsag baseline 6480
After 12 weeks tdf+peg 2b+sim+ntz+artesunate+herbs+vit d hbsag 10500
hbsag after 16 weeks and stopping of all supplements continuing tdf peg and vit d (178ng/ml) = 8543 iu
hbsag after 22weeks(3weeks of peg 2a)= 11776iu(highest till now)
so it is clear that m not responding to ifn therapy but some absurd questions in mind?
shall i continue ifn?
shall i shift back to peg 2b?
surrender and wait for future drugs and till then keep taking tdf?
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