Aa
120 weeks of interferon experience
Dear Studyforhope
I very much need your advice on what should I do?
In 2012 was diagnosed with hep b, hbe-, anti-hbe+, DNA baseline 5000 iu/ml, alt 42 iu/ml, F2 fibrosis (8.1Kpa)
Started treatment with interferon full dose (180) mono. HBV DNA became negative after 8th injection.
My hbsag kinetics as follow all in iu/ml by Architect2000:
W0-10 027 iu/ml
W24-10 785 iu/ml
W48-136.51 iu/ml
W52-35.03 iu/ml
W56-10.9 iu/ml
W60-7.17 iu/ml
W72-1.04 iu/ml
W76-0.21 iu/ml
W80-0.5 iu/ml
W84-0.41 iu/ml
W88-0.28 iu/ml
W92-0.2 iu/ml
W96-0.15 iu/ml
W114-0.3 iu/ml
My hbsag kinetics from w72 till makes me worrying. I doubt I clear hbsag even on W120.
What should I do? Stop interferon or go beyond 120 weeks? Remember you saying it is worth taking interferon as long as hbsag goes down. On the one hand my hbsag is very low and in whole goes down but on the other hand it goes up/down within 0.5 iu range during last 6 month even with interferon. My last 6 month kinetics makes me crazy.
My current Anti-hbsag is 45 mIu/ml (was negative before treatment). My doctor suggest adding Tenofovir.
I very much need your advice on what should I do?
In 2012 was diagnosed with hep b, hbe-, anti-hbe+, DNA baseline 5000 iu/ml, alt 42 iu/ml, F2 fibrosis (8.1Kpa)
Started treatment with interferon full dose (180) mono. HBV DNA became negative after 8th injection.
My hbsag kinetics as follow all in iu/ml by Architect2000:
W0-10 027 iu/ml
W24-10 785 iu/ml
W48-136.51 iu/ml
W52-35.03 iu/ml
W56-10.9 iu/ml
W60-7.17 iu/ml
W72-1.04 iu/ml
W76-0.21 iu/ml
W80-0.5 iu/ml
W84-0.41 iu/ml
W88-0.28 iu/ml
W92-0.2 iu/ml
W96-0.15 iu/ml
W114-0.3 iu/ml
My hbsag kinetics from w72 till makes me worrying. I doubt I clear hbsag even on W120.
What should I do? Stop interferon or go beyond 120 weeks? Remember you saying it is worth taking interferon as long as hbsag goes down. On the one hand my hbsag is very low and in whole goes down but on the other hand it goes up/down within 0.5 iu range during last 6 month even with interferon. My last 6 month kinetics makes me crazy.
My current Anti-hbsag is 45 mIu/ml (was negative before treatment). My doctor suggest adding Tenofovir.
Thank you very much, i kind of thought that, liver was also a bit enlarged so plently of inflammation.
Now it is difficult to choose if:
keep everything like it is now until hbsag und
Or go on protocols like simvastatin, heptech, high dose fish oil and lots of anticancer vegetables to calm down inflammatory state which i guess might slow also clearance
Now it is difficult to choose if:
keep everything like it is now until hbsag und
Or go on protocols like simvastatin, heptech, high dose fish oil and lots of anticancer vegetables to calm down inflammatory state which i guess might slow also clearance
no specific data on this are available to me.
the increased inflammation during peg ifn treatment will be some driver towards genomic instability and push clonal growth forward.
Apoptosis of infected areas will also make space and enhance regeneration from cells already more in the proliferative mode, like the nodules.
in a long standing infection an increasing percentage of liver cells with enhanced genomic change dynamics will also become resistant to hbv infection, it is like a counter evolution. Unfortunately the same cells are also more destabilized towards clonal growth and potential switch to hcc status.
re ifn treatment, it also holds the positive effect of driving some pre hcc cells into apoptosis, so it will increase and decrease hcc risk at the same time.
the increased inflammation during peg ifn treatment will be some driver towards genomic instability and push clonal growth forward.
Apoptosis of infected areas will also make space and enhance regeneration from cells already more in the proliferative mode, like the nodules.
in a long standing infection an increasing percentage of liver cells with enhanced genomic change dynamics will also become resistant to hbv infection, it is like a counter evolution. Unfortunately the same cells are also more destabilized towards clonal growth and potential switch to hcc status.
re ifn treatment, it also holds the positive effect of driving some pre hcc cells into apoptosis, so it will increase and decrease hcc risk at the same time.
do you have any experience on compensated cirrhotic liver with very low fibrosis on peginterferon plus antivirals or monotherapy making no flares and making no fibrosis but making new regenerative nodules or doubling the size on the preexisting ones (but sizes < 1cm)?
the response is towards low hbsag and slow clearance on follow up, can cytokines and inflammation be so bad on the nodules or increase hcc risk despite normal alt?
in pisa they had another case like this from a normal liver turned into full of small nodules from peg plus adv plus lam.that patient also had hbsag clearance and nodules slowly cleared in a decade
You may also try dr coimbra protocol of high dose vit d3 and goleic gcmaf added to peg.i sent you a pm about it
that's just fine... are you based in Russia? is this a trial?
If you do not mind me asking how old are you? what's your BMI? do you play any sport?
If you do not mind me asking how old are you? what's your BMI? do you play any sport?
Dear Studyforhope
Please find my fibroscan data below:
W0 - 8,1 Kpa
W24 - 7,6 Kpa
W38 - 6,8 Kpa
W48 - 6,8 Kpa
W76 - 6,8 Kpa
W96 - 5,5 Kpa
I started using fibroguard on 24th week and stopped on 48th week. Do not know how much fibroguard is responsible for fibrosis regression. From my experience interferon alone worked pretty good for me. I can not say that I changed my diet much but of course no junk food which I never even before.
As for:
"however the intrahepatic cytokine profile also was, at least at some time in the past, causing inflammation and activating fibrosis forming stellate cells."
This maybe due to alcohol because I used to be everyday social drinker for a couple of years before I was diagnosed. So maybe that was main driving force for fibrosis.
Please find my fibroscan data below:
W0 - 8,1 Kpa
W24 - 7,6 Kpa
W38 - 6,8 Kpa
W48 - 6,8 Kpa
W76 - 6,8 Kpa
W96 - 5,5 Kpa
I started using fibroguard on 24th week and stopped on 48th week. Do not know how much fibroguard is responsible for fibrosis regression. From my experience interferon alone worked pretty good for me. I can not say that I changed my diet much but of course no junk food which I never even before.
As for:
"however the intrahepatic cytokine profile also was, at least at some time in the past, causing inflammation and activating fibrosis forming stellate cells."
This maybe due to alcohol because I used to be everyday social drinker for a couple of years before I was diagnosed. So maybe that was main driving force for fibrosis.
I am happy that you don't have side effect from interferon. I am also on interferon for second time. I am tired all the time and my skin look yellow, maybe because my wbc are 4 and platet 120. Also this year u got 2 times flu:(
very good results Andrey19, congrats !
"You would however have to monitor fairly frequently after ifn stop to catch a rising reinfection before it has reached dangerous levels that are hard to reduce. Your fairly high fibrosis level also warrants caution, do not let a flare occur."
Studyforhope, does this apply to my situation too, where i have 380k hbsag quant, but never took treatment or is after the treatment ?
Thank you
"You would however have to monitor fairly frequently after ifn stop to catch a rising reinfection before it has reached dangerous levels that are hard to reduce. Your fairly high fibrosis level also warrants caution, do not let a flare occur."
Studyforhope, does this apply to my situation too, where i have 380k hbsag quant, but never took treatment or is after the treatment ?
Thank you
yes, tenofovir would stop a flare from developing if you catch it in time.
I would limit the DNA increase to below 3000 iu. You had a low starting level - 5000 iU before starting ifn, that is good and shows that your immune mechanisms had fairly good control over hbv replication. However the intrahepatic cytokine profile also was, at least at some time in the past, causing inflammation and activating fibrosis forming stellate cells.
It is not likely that you develop a flare, considering the bigger picture, after ifn stopping you might just experience a slow rise in hbsag levels. Or it stays at this very low level for a longer time, it is hard to predict. With thymosin alpha it was more common than with ifn , that delayed clearance and immune stabilization effects occurred.
However Caucasian genoptype A patients experienced delayed high % hbsag losses after ifn treatment over a period of 5 years, those were adults aquired infections of relatively short durations of chronicity.
You might consider, since you dont seem to suffer major ifn side effects to stay on it for another 6 month.
The thymus is constantly producing new naive Tcell precursors, if you are lucky, a capable one might come up in this time and turn you around for complete hbsag loss and higher AB titers.
Your new fibroscan value is quite encouraging. Can you tell us at which period you were taking the fibroguard formula and if that could have contributed to this improvement?
I would limit the DNA increase to below 3000 iu. You had a low starting level - 5000 iU before starting ifn, that is good and shows that your immune mechanisms had fairly good control over hbv replication. However the intrahepatic cytokine profile also was, at least at some time in the past, causing inflammation and activating fibrosis forming stellate cells.
It is not likely that you develop a flare, considering the bigger picture, after ifn stopping you might just experience a slow rise in hbsag levels. Or it stays at this very low level for a longer time, it is hard to predict. With thymosin alpha it was more common than with ifn , that delayed clearance and immune stabilization effects occurred.
However Caucasian genoptype A patients experienced delayed high % hbsag losses after ifn treatment over a period of 5 years, those were adults aquired infections of relatively short durations of chronicity.
You might consider, since you dont seem to suffer major ifn side effects to stay on it for another 6 month.
The thymus is constantly producing new naive Tcell precursors, if you are lucky, a capable one might come up in this time and turn you around for complete hbsag loss and higher AB titers.
Your new fibroscan value is quite encouraging. Can you tell us at which period you were taking the fibroguard formula and if that could have contributed to this improvement?
Dear Studyforhope, thank you very much for the answer.
"You would however have to monitor fairly frequently after ifn stop to catch a rising reinfection before it has reached dangerous levels that are hard to reduce. Your fairly high fibrosis level also warrants caution, do not let a flare occur."
By rising reinfection you imply hbv dna relapse to high levels? Am I right? but in case I add Tenofovir there should be no chance for relapse while my quantitative hbsag titer is a big question after withdrawal of interferon?
As to my fibrosis it was 8.1Kpa at baseline now it is 5.4 Kpa.
Another thing I have noticed is that my ALT level dropped and is fluctuating around 22-27 for the last half year after hbsag titer felt below 1 iu/ml while ALT used to be around 57 on average before drop.
"You would however have to monitor fairly frequently after ifn stop to catch a rising reinfection before it has reached dangerous levels that are hard to reduce. Your fairly high fibrosis level also warrants caution, do not let a flare occur."
By rising reinfection you imply hbv dna relapse to high levels? Am I right? but in case I add Tenofovir there should be no chance for relapse while my quantitative hbsag titer is a big question after withdrawal of interferon?
As to my fibrosis it was 8.1Kpa at baseline now it is 5.4 Kpa.
Another thing I have noticed is that my ALT level dropped and is fluctuating around 22-27 for the last half year after hbsag titer felt below 1 iu/ml while ALT used to be around 57 on average before drop.
Steff, frankly you were the one who inspired me to start with interferon 2,5 years ago. Much thanks to you man! Despite high titer of hbsag at the baseline my final result is pretty good but still not enough. I tolerate interferon very well and got used to living with weekly injections. Now very hard to decide to stop treatment with interferon.
If you have enough resources and your doc collaborates with you, you could make an attempt to increase anti hbsag levels and t cell responses by using a therapeutic vaccine. You can combine the standard surface antigen vaccine with HBV core particles that you obtain from a biotech supply company and use the mix together with thymosin alpha, which might be obtainable in Russia. Thymosin alpha is known to boost hbsag vaccine responses.
Your situation is not unusual, it seems that in the process of reducing cccDNA and infected cells a certain low level is reached that the current elimination mechanisms cannot overcome.
Looking at abstract 1855 from the AASLD 2014, one explanation would be that the small amount of genome integrated sequences keep producing hbsag that is not from a cccDNA template. Unfortunately some of these integrations will also be full genome, in a transcriptionally active spot, so reinfection and spreading is possible aside from the hbsag production.
The crux with the isolated hbsag integrations is that they are extremely hard to eliminate even with a good class 1 T cell response, since the surface antigen as a membrane protein has no cytosolic presence and therefore no work up in the PROTEASOMES for class 1 MHC epitope presentations. In other words, this isolated protein is almost invisible to the T cells. Thus, paradoxically, even if you have hbsag class1 specific CTLs, they won't be able to detect those cells.
While the small amount of isolated integrated hbsag production as such would not harm you, it's really nasty effect is that it limits the available level of anti hbsag by complexing and competing, so that the protection against reinfection spreading by covering and complexing de novo produced virions becomes weak and ineffective.
From a practical point of view, starting tenofovir would prevent any flare up of the infection, but it is unlikely to push you over into complete hbsag negativity.
It is entirely possible that the long Ifn treatment has helped to establish enough of a protective T cell population that it could keep the infection spreading under a more permanent control.
You would however have to monitor fairly frequently after ifn stop to catch a rising reinfection before it has reached dangerous levels that are hard to reduce. Your fairly high fibrosis level also warrants caution, do not let a flare occur.
Looking at abstract 1855 from the AASLD 2014, one explanation would be that the small amount of genome integrated sequences keep producing hbsag that is not from a cccDNA template. Unfortunately some of these integrations will also be full genome, in a transcriptionally active spot, so reinfection and spreading is possible aside from the hbsag production.
The crux with the isolated hbsag integrations is that they are extremely hard to eliminate even with a good class 1 T cell response, since the surface antigen as a membrane protein has no cytosolic presence and therefore no work up in the PROTEASOMES for class 1 MHC epitope presentations. In other words, this isolated protein is almost invisible to the T cells. Thus, paradoxically, even if you have hbsag class1 specific CTLs, they won't be able to detect those cells.
While the small amount of isolated integrated hbsag production as such would not harm you, it's really nasty effect is that it limits the available level of anti hbsag by complexing and competing, so that the protection against reinfection spreading by covering and complexing de novo produced virions becomes weak and ineffective.
From a practical point of view, starting tenofovir would prevent any flare up of the infection, but it is unlikely to push you over into complete hbsag negativity.
It is entirely possible that the long Ifn treatment has helped to establish enough of a protective T cell population that it could keep the infection spreading under a more permanent control.
You would however have to monitor fairly frequently after ifn stop to catch a rising reinfection before it has reached dangerous levels that are hard to reduce. Your fairly high fibrosis level also warrants caution, do not let a flare occur.
go on with it, there are trials of continuous peg for 5 years on responders and also hdv has a protocol of long peg
what is your vitd25oh and intact pth?i think adding zadaxin maybe the best or maybe also adding tdf
what is your vitd25oh and intact pth?i think adding zadaxin maybe the best or maybe also adding tdf
feel just fine, I would say nothing worries me. My WBC is just within normal range, PLT is always around 90-100 (lower than normal).
this is unbelievable!!! 120wks full dose??!!! are you experiencing sides? what is your wbc and platelets count? how are u feeling?
WOW! 120 months on interferon?! My hat is off to you. I did 48 weeks and barely made it. I just happened to see your post and wanted to say good job. Have you been on a high dose for 120 weeks? Sorry your numbers were not clear to me. Your fibrosis is pretty low which is good. I am sure someone with more knowledge than I have will be a long. I just wanted to congratulate you for sticking with it.
Take Care, Dee
Take Care, Dee
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