Who will be cured first, hbeag postivie group or hbeag negative group?

[itac]

And how soon after one group is cured, will they be able to cure the other group?
Taking bets now.

[needadvicewithhep]

For me as a patient i would only want a liver transplant as a last resort...


Even if I had a transplant and erradicated the cccdna  i would rather not have it. Can you imagine the practicalities of living with that. Dont get me wrong look at Eric Abidail but still I would like to try and keep my own liver if possible

[itac]

Ofcourse... Liver transplant is no walk in the park...

[studyforhope]

If you take strong antivirals before and after the transplant you have a good chance that the reinfection will spread very very  slowly. But once you stop the antivirals chances are high that a rebound will occur.

[itac]

Oh really I didn't know that... That kinda disappoints... I guess seroconversion and liver transplant is better... Then you have the real deal... Although probably not very practical...

[itac]

But wait... I thought you can get a liver transplant and not be seroconverted and still not have the virus in the new liver, because you can take strong antivirals regime before the transplant, during it and after...? Isn't it how they prevent a vertical transmission e.g. from mother to baby?

[studyforhope]

Yes, but if you are seroconverted, the blood virions will all be coated with antibody and cannot infect and enter any liver cell.

[Royal36]

I can answer the last part of your question even after the liver transplantation the virus will not go away because it is still in the blood.

[studyforhope]

Ultrasound monitoring guidelines are developed by statistic considerations and cost benefit ratios. Clearly a fresh infection is much less likely to develop HCC and general cancer propensity as a function of age will have a clear  influence. Some insurances pay only for once a year screening. The 6 month rules were developed in consideration of the typical speed of growth of a fresh HCC. Within 6 month they are typically small enough that treatment techniques like alcohol injection, radio ablation  or arterial embolization will cure the current HCC growth. Most screenings are obviously negative. Most HCCs further develop from cirrhotic livers, thus it is all a question on how to handle the risk.

DRACO is a technique to oligomerize caspases that get activated in the presence of double stranded RNA. HBV does not produce ds rna, beyond that it is wait and see,  

If you get  a liver transplant after you have seroconverted the hbsag, chances are very high that the new liver will not get infected.
Patients with liver transplants should have a fairly normal life expectancy,  maybe the anti rejection medications predispose them for certain infections, since they are tcell suppressing.

[itac]

When you say a person who seroconverted still needs to monitor with Ultrasound every 6 months... Do you refer to people above the age of 40? Or even young people should monitor? How likely it is that a person below 40 would develop HCC because of integrated cells? Some doctors even suggest to monitor only after a person who is hbsag positive only after the age of 40, are they all wrong?

Also, what do you think about DRACO that is developed by the MIT already 10 years, does it have the potential to be the next antibiotics for viruses? https://www.ll.mit.edu/news/DRACO.html

I just can't comprehend that you can't cleanse all the cells in the liver to get rid of the genetic material from the virus. Are you saying even Timothy Brown who got cured from hiv is still in higher risk of cancer because there is some latent virus in his immune cells? Well, technically our body might have many viruses like herpes, bar espstein, they all have potential  to cause problems or cancer, but it's a question of how likely it is... and if there is a way to reduce the risk by doing something... Btw, if getting a new liver... Would that ensure you will have no virus anymore? Also, how safe is it to get a liver transplant, and how long can you live with it after the transplant has happened.

[studyforhope]

Even birinapant will not wipe out the last infected cell within the ten trillion cell liver.
in chimp studies it was demonstrated that a single hbv virion was able to start the infection.
We will have to rely on reinfection protection by the antibody and the immune surveillance by the class I t cells.

Birinapant holds the promise to eliminate large amounts of cells with integrated surface antigen gene fragments, often the starting point for HCC.  Thus it should also have a great HCC prevention power, if it will ever make it to approval.

[itac]

Also is there something that at least identifies the infected cells, like is there a double stranded RNA on every infected cell? Something that the DRACO drug was supposed to target and I believe biripriant too... Can you use some advanced imaging technique with contrast to be able to highlight the infected cells in an image? If such image could be produced could it be possible to direct drugs to attached only the highlighted zones? Something I believe scentists are trying to do with hiv latent cells (so the technology could be borrowed once completed)

[faithhopegod]

That is a good question...

[needadvicewithhep]

Even a combination of NAPS + Birinpant used i  a sequential manner wouldnt represent a good chance of cccdna eradication?

[needadvicewithhep]

Even a comb

[faithhopegod]

That would be great if they could sterilize it..

[studyforhope]

These inhibitors are never 100% effective. It is extremely unlikely that a complete sterilizing cccDNA removing method can be found.

almost all acute hbv patients  that spontaneously cure BTW have small amounts of circulating virions in their plasma but they are complexes and cannot reinfect.

There is hardly a method to check that the whole liver is completely  ccccDNA free..

The key is the neutralizing antibody and also a memory tcell response that is very sensitive and tends to reduce clusters of viral regrowth that might occur despite the antibodies presence.

What arbutus is referring to is a goal of reduction to a manageable remnant.

[studyforhope]

Even an acutely self cured former hbv patient has a high chance to reactivate viral spread and acute hepatitis if treated with chemotherapy or strong tumor necrosis factor alpha agonizing drugs. Antiviral prophylaxis is indicated in all these cases. Unfortunately this knowledge is sometimes absent in treating oncologists and rheumatologists.

Cells with integrated hbv sequences in critical genomic areas controlling cell division and safeguarding against cancerous transformation are most at risk to develop the cancer phenotype,in particular if intense replication and inflammatory oxidative stress causes additional progression towards the concerns restructuring of the hepatocyte genome.

If most infected and integrated cells have died, the HCC  risk will be substantially decreased, but never reaches the background uninfected level.

Thus continousl 6 month ultrasound monitoring is still required even in hbsag seroconverted patients.

[itac]

Oh I didn't know after you hbsag seroconvert you still need to monitor every 6 months with US... That *****.... Would be ever possible to eradicte all cccDna from the cell? I see Arbutus HBV Assets include: cccDNA Formation Inhibitors "reduce the amount of cccDNA in infected liver cells and could ultimately eliminate the reservoir of HBV genomic material required for continued viral replication"
And
"cccDNA Epigenetic Modifiers".
Is there any hope that Arbutus or another company will be able to completely eradicte the virus reservoir from all liver cells to bring it to uninfected level? If so, how would they be able to confirm that they indeed got rid of all of the reservoir? Thanks for the informative answers.

[studyforhope]

If 10000 hepatocytes would die and getting replaced every year it would mean that one out of a billion hepatocytes would get replaced per year. That is a very low replacement rate for an effective cleanup..

Total liver cell number is about 10 trillion. All mechanical considerations must take this gigantic number into account. Total cleanup is indeed quite impossible for hbv.

[itac]

How likely these cells to cause cancer in the long run? Since they malfunction regular cell function?
Also, should a seroconverted always worry in the future where if he might have cancer and will receive chemo or for the event his immune get weaker, that the virus will come back?

[studyforhope]

In a liver with low inflammation, the hepatocyte turnover is quite slow.A cell with cccDNA can loose that hbv dna or it can be redistributed  to the daughter cells.

At the so called functional cure there is a very very small number of cccDNA containing liver cells left, also likely a small number of cells with hbsag integration only. The total production of hbsag by these two sources must be small enough that the constantly produced  hbsag antibody can neutralize this completely and still have a good titer left after that so that it's major function to grab and neutralize remnant produced Dane particles is effective enough to prevent a respreading of the infection to other cells.

[itac]

studyforhope, if someone gets functionally cured meaning he hbsag seroconverted, what will happen to the cells with cccdna? will the cells will be replaced by new cells and the cccdna will die? if so, what is the rate this happens? e.g. 10,000 hypocytes die and getting replaced every year.
Or can cccdna infected cells can persist for year cause they send signals to the cells not to die?
Thanks!

[itac]

Also, how likely the remaining cells can still cause cancer?

[sorte]

thanks Stef ! :)

[stef2011]

i emailed the cuban institute for info on hbv vaccine, hopefully they will answer with dates

[stef2011]

definitely not important the little undetectable cccdna left once immune system takes care of it and blocks any possible reinfection...we, hbv carriers, just need a functioning immune system towards hbv

[needadvicewithhep]

It would show
hbsag negative
hbeag negative
Hbsab positive
Hbeab positive

That would mean functionally cured the cccdna would remain but from a patients perspective who cares about that unless they have chemo

[faithhopegod]

My doc told me once you're clear from heb c is just shows negative.

[faithhopegod]

So what is exactly is a cure if its the virus is inside the core? Is it the elimination of the virus inside of the core so when you get a next blood test would it still show you had an infection in the past?