The things I read about hbv integration is really scary, continuous hbv integration is a road to liver cancer… we really need a better medication to stop this integration
I guess the higher the viral load, the higher the hbv integration…is that right
Dear @chigoziekingsley5454 ,
If your viral load has not changed since last year and your ALT is still normal (you can check your test results for this), you have partial cure of BV (we also call this inactive HBV infection).
The virus is replicating but at low levels. We know that with partial cure established that the risk for HCC is lower than for someone with chronic HBV infection but of course not as low as with functional cure.
I do not think should be so anxious about his problem but I do think you should discuss this with your doctor.
@availlant , @ThomasTu , @john.tavis
I have one question here, in all the discussions I see the quantity of HBsAg is the one that matters for cure due to the sleep of the immune system by HBsAg.but I want to know why, for those who have low quantities like 10, 20, and 30 by treatment like siRNA or without treatment by the natural process of the disease, the immune system can not control or clear. what did you recommend for one who is not on treatment but the quantity of surface antigen is like 10 or 20?
Dear @lemlem ,
We know from studies with pegIFN that functional cure requires HBsAg to be < 1 IU/mL (typically at least a 4 log reduction from baseline). Even HBsAg at 10 IU/mL is a significant amount of HBsAg. This only happens rarely with siRNA.
From the get go, the siRNA mechanism leaves a significant portion of target mRNA intact (this has been demonstrated for numerous other host targets in the liver in clinical studies) so this approach can only reduce antigen expression, not eliminate it. As such it is not surprising that all siRNA approaches have failed to date, even in combination with other therapies. Additionally, it is clear from numerous clinical data that siRNA functionality rapidly disappears (or is absent before therapy) in patients due to pre-existing or the rapid development of escape mutations. However, off target immunostimulatory properties of siRNA maintain HBsAg reduction by activation of innate immunity via TLR3. This means that HBsAg produced from subviral particles is largely unaffected. This has also been shown in clinical studies.
If you are not on therapy and have HBsAg in this low range, you may have partial cure but we need to know what your latest HBV DNA and ALT levels are.
@availlant ,
as always thank you very much for responding even on weekends,
yes I am not on treatment and have never been either, and my surface antigne is around 18.6 and DNA is around 26,000, ALT is 43 . note DNA and ALT tests are before 2 months and surface antigen test is before 3 days.
Dear @lemlem ,
With this level of HBV DNA (even with almost normal ALT) you may want to consider discussing antiviral therapy with your doctor.
Best regards,
Noted @availlant , i will do,
thank you again
BR
My understanding with HBV integration is that only part of the whole HBV genome is integrated, so integrated hbvdna cannot reproduce the whole HBV virus. However, if the site of integration in the human genes can increase risk of cancer, then it is very bad. Also, part of the integrated hbvdna may produce mRNA for the HBV surface antigens, resulting in production of surface antigens which when released into the blood stream can suppress the immune system to fight and control HBV. So, integration is bad and should be reduced by medication if necessary.
It seems like it was terminated early due to lack of efficacy: https://www.postersessiononline.eu/173580348_eu/congresos/ILC2022/aula/-SAT_446_ILC2022.pdf
Disappointing. The method of action sounded particularly enticing on this one
I’m not sure why they tested this compound in HBeAg-negative patients, where most of the HBsAg is coming from integrated HBV DNA (which likely does not rely on HBx-mediated transcriptional regulation)… This seems like a real weakness in the study and it may have better efficacy in HBeAg-positive patients.
Is there any test that can calculate how many integrated hbv in the liver cells, so know possible treatment regime
Hi @MARIAN,
Just putting this with the other discussion about new HBV drugs. This is a new CAM, which inhibits viral replication.
Thomas
hello, friends! I hope everything is well with everyone!
Does anyone have any information about this medication that is apparently being tested together with bepirovirsen? Which type? How does it work in the body?
Dear @La.sciamachie ,
Unfortunately, this is another name switch which is very confusing for patients.
ARO-HBV was one of the earlier generation siRNAs tested in HBV. It was licensed from Arrowhead Pharmaceuticals by Johnson & Johnson in 2018 and renamed JNJ-73763989 (or JNJ-3989 for short). Prior to J&J abandoning its entire HBV portfolio in 2023 for JNJ-3989’s inability to achieve functional cure in combination with various agents, it was given the generic name tomligisiran. This drug was in turn licensed by J&J to GSK who assigned its own internal compound name to it (GSK-5637608) and changed its generic name to daplusiran.
So there is nothing new about this compound and no data to suggest its promise. Titles like this are very misleading.
Thanks for the explanation, dr. @availlant
I found the news strange because I had never seen the name of this drug before.