Very interesting article. Fast track? Does it mean that certain people will get the approval?
@availlant Your thoughts?
Hi @Nass
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Thank you! Is 1500iu HBSAG consider low base or mid?
Dear @Nass ,
A baseline HBsAg of 1500 IU/mL is low. The average baseline HBsAg is ~ 10,000 IU/mL and can be < 125,000 IU/mL in HBeAg positive chronic HBV infection or during acute HBV infection.
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As always… Thank you so much!!
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Hi @ThomasTu ,
If we can’t target cell with cccDNA, then why don’t we take minimum low dose medication (and hopefully with no side effects) to stop virus till all the liver cells that are infected with cccDNA are all exhausted (converted into virus or die before conversion) and virus is killed/disabled outside cells before it has chance to infects new liver cells?
I know we have antiviral to achieve this but does cccDNA stays present in cells forever? Do we know how long it takes for an infected liver cell to die naturally and continue medication double that time? Does the B virus only affect a particular type of liver cells?
Thanks
Hey Aman,
I read somewhere on here that cccDNA gets deleted when a liver cell undergoes Mitosis (cell division), and the two new liver cells does not have any cccDNA. However, some liver cells (potentially containing cccDNA of the Hep. B Virus) does not divide. We are not sure how long cccDNA will remain active in a non-dividing liver cell. It could also be that since Hep. B virus are replicated in the liver and also infects liver cells, it may have an easier time staying in the liver.
Liver cells as far as I understand are some of the most actively replaced cells in our body, I could be wrong on this one though. It would be nice to hear from some other community members who have been on anti-virals for a long time and see what their experiences have been.
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Welcome @Jay
I’m glad you have found us and shared your story.
It is very scary and uncertain future. Your head must be whirling with questions and terror.
Please, we are here for you. Your life is important for your family’s happiness. They don’t care if you have an illness. As long as they can hug and love you is all that matters.
You are unlikely to have past on to your son and maybe even your wife.
Get them tested and vaccinated as @availlant has said.
You can still have a long and healthy life. Read some of the subjects and stories. I’m sure you’ll find they are similar to yours.
One day at a time.
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Thank you @A7xImpulse
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Great question, @Aman. And thanks @A7xImpulse for a great summary of the most recent research (which we have published on Mitosis of hepatitis B virus-infected cells in vitro results in uninfected daughter cells - ScienceDirect and has been highlighted by a PhD student working in my lab - Example entry: Hepatitis B cccDNA viral reservoirs - stubborn nails in the quest for a complete cure). I am really so glad that we’ve been able to get such sophisticated complex concepts taken up by the community.
Some additional comments:
The average lifespan of a liver cell is about 6 months, which is fairly long when you think about it. This is why the reduction of cccDNA even while on therapy is very slow.
At the start of an infection (immune tolerance phase) pretty much the entire liver is infected. But when you are in HBeAg-negative phases, something like 1% of liver cells are infected (even when there’s plenty of virus around to infect the other cells). We still don’t know the underlying reason for this and if the one that are infected really represent a different type of cell.
Indeed, I’ve been on antivirals for many years and my levels of HBeAg and HBsAg have remained quite high through the years.
Thomas
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Visited the drug watch page under the Hep foundation. But it’s always a bit hard to interprete. Like how many drugs for functional cure or above are at final stage testing? Or application for approval?
The only one thats in Phase 3 right now (and fast tracked by FDA) is Bepirovirsen from GSK. Other than that, VIR has some clinical trials in Phase 2 that are showing decent results so far. And Replicor (NAPS) is in phase 2 as well.
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I know a couple of people here were enrolled in the Arbutus clinical trial with Peg Interferon or VTP-300. How is that going for you in it? Somebody posted an abstract for the trial coming up this week at EASL conference, results look a little promising too although its EOT data mostly, not post 6 months for FC. To all the experts on here, what do you all think about the data?
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Which drug can direct inhibit integrate of hbv DNA into liver cells
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There is current no agent in development that directly blocks the integration of HBV DNA into host chromosomes. This is very unlikely to occur since the enzymes which direct this process are also critical for DNA repair of host chromosomes.
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Hi @Mike2,
I was at EASL, but didn’t manage to catch that presentation. I’ll have a look for it in the recorded sessions and report back.
Cheers,
Thomas
While @availlant is correct that no drug likely inhibits integration directly, you can prevent new integrations by ensuring double-stranded linear forms of the virus do not enter the nucleus.
So, essentially any drug that inhibits new infection events or establishment of new cccDNA is likely to also inhibit new integration events. These might include entry inhibitors (we have shown this in some of our in vitro studies), capsid inhibitors, siRNAs, NAPs, etc. Even entecavir and tenofovir likely have some effects on integration rates (this has been reported in some papers in patients). However, existing integrations are much more difficult to get rid of and the reduction of these over time is very slow.
Hope this helps,
Thomas
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Yes Thomas is right here…
One of reasons we encourage everyone to start antiviral therapy as soon as possible is to slow down the rate of HBV DNA integrations as much as possible. These HBV DNA integrations and their accumulation over time during untreated chronic HBV infection drive the onset of liver cancer. All approved NUC therapies (3TC, ADV, ETV, TDF and TAF) do this as Thomas has mentioned - although ETV and TDF / TAF are really the preferred first line NUC therapies now.
Unfortunately, the only way to efficiently remove liver cells with intergated HBV DNA is via their removal by the host immune response. Additionally, because integrated HBV DNA only produces HBsAg efficiently, this requires a HBsAg-specific immune response.
The first step in allowing a potent HBsAg-specific immune response is to clear HBV subviral particles (99.99% of circulating HBsAg) from the blood. Then very likely additional immunotherapy will be required to wake up this HBsAg-response which in most patients has been put asleep by long exposure to HBsAg in the blood.
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Sir my DNA level was 530 last year, January my liver function tests was normal, please can I start antiviral drugs to prevent this hbv integration, am really scared of liver cancer…help me