Has genotype been a factor in those that have had success?
Karen
Dear @klrway
To date the only therapy that has demonstrated high rates of stable functional cure (56% at > 5 years treatment free follow-up) has been TDF + pegIFN + NAPs (REP 2139-Mg), an effect which occurs regardless of baseline HBsAg levels or HBeAg status .
The antiviral effects of NAPs, bepirovirsen and GalNAc-siRNA have been shown to be genotype independent.
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Does anyone have new information about the start of clinical trials for Thervac B? On the website it says they would start them in January this year.
Thank@joan block…this adds me hope and strength more especially after I was hit hard by the unfortunate death of our own kitoni from whom I attained much strength coz of his continuous advice.
Dear @La.sciamachie,
As far as I know, the trials for Thervac B had been delayed:
I’m not exactly sure where they are situated at the moment.
Thomas
When someone has a functional cure for hepatitis b, will he or she still test positive for hbsag…
What hope do we have about the bepirovirsen drugs that will soon be available for use
It is a vaccine that they’re trying to develop, you know vaccine takes alot of time before is made available for use… firstly let’s hope on the GSK bepirovirsen which has a potential for functional cure for chronic hepatitis b
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So is there no hope for bepirovirsen to be made available for use…but they said it has 33% functional cure rate
Dear @chigoziekingsley5454,
Bepirovirsen is not a vaccine but it does work by stimulating the immune system. The latest data we have is the functional cure is present in 9% of patients who have received bepirovirsen (this number will likely decline) but unfortunately these patients are those rare patients with low HBsAg before treatment.
Certainly additional clinical trials will be required to see how bepirovirsen will work in the general population.
Dear @availlant , my heart is deeply grateful for the attention you give us
I, as a layman, and a chronic patient for a short time, was filled with hope with this market movement for the acquisition of the jnj-3989 by GSK… even more so due to the huge amount involved.
However, the assessment of those gentlemen who have knowledge of what is actually being attempted keeps us in the reality of things as they are. Despite this, knowing that things are not simple, I still retain some hope that they can find a combination with analogues for a sustained and safe functional cure.
Hi @chigoziekingsley5454, functional cure is defined as the persistent loss of HBsAg in the blood, so they should not test positive for HBsAg.
Thomas
Hi,
I think liver damage happens as a result of immune response to virus. If these new medicines such as bepirovirsen activate immune response, will it impact liver function or cause liver scarring?
Thanks
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Hi @Aman ,
Yes a very good question!
Liver inflammation is indeed caused by immune responses to viral replication in the liver. In chronic HBV infection, liver inflammation is often suppressed (by HBsAg) so that infection can persist for many years with out evidence of liver inflammation. This is one of the reasons why only a small fraction of people with HBV infection get diagnosed.
Persistent liver inflammation causes scarring (fibrosis) which if left unchecked can lead to more severe liver disease (cirrhosis). While this is caused by the infected cells in the liver, this chronic inflammation can effect the healthy cells of the liver as well. The purpose of existing drugs for HBV is to stop viral replication so that liver inflammation disappears. Unfortunately, these drugs to not target the production of HBsAg, which is why they are life-long therapies.
Although immune function drives liver inflammation, in order to restore effective immune control of HBV infection in the liver (we call this functional cure), we have to correct two important problems caused by HBV infection:
- Remove the ability of the liver to produce HBsAg (which prevents immune control of HBV).
- Re-awaken the immune responses to HBV infection which have been “put to sleep” by long term exposure to HBsAg.
For this reason, any approach successful in achieving functional cure will have to achieve both of these actions (and thus require an immunotherapy).
In the case of bepirovirsen, its immunotherapeutic effects appear to be able to achieve #2 above and perhaps even #1 but these immunostimulatory effects are quenched by HBsAg so this drug only shows significant activity in patients with low levels of HBsAg present. There are no data in the current clinical trials ongoing to suggest that these immunostimulatory properties are accompanied by changes in liver function or that they introduce liver scarring.
It is important to note that functional cure will always require the establishment of immune control. This actually occurs in the 75-80% of patients who self resolve their acute HBV infection, most who never show signs of this immunological “battle”. Even in those people who rarely achieve functional cure with current therapies (including more often with the approved immunotherapy pegylated interferon) the clear signs of reestablishing immune control are not accompanied by changes in liver function. The reason for this is that only infected cells in the liver are likely targeted by these immune functions, leaving healthy liver cells intact.
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Hi @availlant,
You mention that high HBsAg levels in the blood prevents the immune system of CHB patients from recovering from immune exhaustion to Hep. B virus. Can you elaborate on how much HBsAg in the blood measured from a HBsAg Quantitative test is considered too high, and would render any immune-stimulating treatment ineffective to “restart” natural immune control of the virus? Does the level of HBsAg in the blood fluctacte greatly within the day or does it stay somewhat consistent for an individual?
Thank you.
Dear @A7xImpulse ,
A very good question.
Using clinical data from the most widely used immunotherapy to date, pegylated interferon, we see that there are large differences between functional cure rates in patients with more than or less than 1000 IU/mL HBsAg at the start of treatment. Generally speaking pegIFN functional cure rates at < 1000 IU/mL of HBsAg can be up to 30% while functional cure rates above 1000 IU/mL HBsAg are < 6%. This also appears to be case for other immunotherapies in development like bepirovirsen. It could be that the “sensitivity” to HBsAg inhibition is different for different drugs which employ different immunosrtimulatory mechanisms but overall the rule still appears to be holding.
HBsAg in the blood is almost entirely derived from non-infectious subviral particles which are not targeted by currently approved oral antiviral therapies for HBV. For every virus there are approximately 10,000-100,000 subviral particles. HBsAg is continually produced from liver cells and is recycled by the liver over a period of a few days. The levels of HBsAg in the blood are fairly constant and reflect a balance between the persistently abundant production of these subviral particles and their rapid clearance from the blood.
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Thank you @availlant for your response.
CHB is a very challenging problem to solve by the looks of it, I am hoping that more funding could be made available to tackle this problem. CHB is an additional source of stress that compounds other challenges in modern life.
There are very few open source scientific studies published on HBsAg, most are behind a paywall. What is the mechanism behind the rapid clearance of HBsAg from the blood when not enough anti-bodies for the subviral partials are produced? Isn’t our Liver the organ responsible to eliminate virus particals from our blood (the irony)?
Thank you.
Dear @A7xImpulse ,
Subviral particles are produced as a high density lipoprotein (HDL) which has the same composition as normally produced HDL in your blood except that it also contains HBsAg. It is likely that the HBV has evolved to hijack this lipoprotein secretion mechanism present in a class of liver cells whcih are responsible for lipoprotein recycling called hepatocytes to produce such large amounts of HBsAg. As such, the antibody independent recycling of HBsAg also likely occurs by the same mechanisms hepatocytes use to recycle HDL. These are the cells in the liver which are (ironically but not accidentally) also infected by HBV.
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Good every one my name is jay I just did a full blood test and I was diagnosed of hep b chronic I’m so scared right now I don’t know what to do I live in Ireland but I have an appointment to see a specialist on the 5th of march I’m scared right now and my family is back in Nigeria I’m scared of them as well because I feel I have also exposure my wife and son to this I planned a beautiful family but this now as taken away my joy I don’t know what do I am glad I found this platform I need advice because I’m scared of my family losing them and even my self anytime I see my son picture I just want to end my life this my test result below can some one explain this to me I’m so tired
HBsAg(Architect) positive
Anti-HCV(Architect) negative
T.pallidum Total (Architect) negative
HCV Ag(Architect) negative
Anti-HBe(Architect) positive
HBeAg(Architect) negative
Anti-HBc lgM (Architect) negative
Anti-Hbc total positive
Anti-HDV total (liaison)negative
Please can some explain this to me my heart is so heavy I feel my life counting by the day
Dear @Jay ,
We are sorry to hear of your recent diagnosis but please do not be scared for yourself or your family. Please have hope - things will be all right for your and your family. Your HBV infection is not your fault. Most people with chronic HBV infection also do not know they are infected (often for decades). You still have your beautiful family - do not despair!
There are good medications which will safely control your viral infection and will allow you to live a long and happy life. Here are some “next steps” for you:
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Keep your appointment with your specialist in Ireland. You are missing some important tests which include HBV DNA and ALT and perhaps some imaging of your liver. These will help the specialist decide how to approach your antiviral therapy.
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You have to discuss your diagnosis with your wife. HBV infection is most frequently transmitted by sexual intercourse or from mother to child during birth. Your wife should get tested as soon as possible.
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The likelihood of you transmitting your HBV infection to your son is small. Nevertheless, he should also get tested as soon as possible.
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If your wife and son test negative for HBV, they should get vaccinated as soon as possible. When your antiviral therapy is actively suppressing your liver infection and they have been vaccinated, the risk for transmission of infection will be almost zero.
Please let us know how things are going. You are not alone.
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