The action of spirulina appears to be imunotherapeutic and is likely driven by the stimulation innate immunity see here.
In this study, the effect of spirulina appears to be very mild (0.3 log10 IU/mL over 6 months) with most of this reduction confined to patients with very low baseline HBsAg (~100-500 IU/mL).
These reductions are likely coming from very mild inactivation of cccDNA and very likely do not touch the production of HBsAg coming from integrated HBV DNA.
We know from studies with pegIFN that functional cure only occurs with HBsAg reduction to < 1 IU/mL during therapy.
I do not see any harm in adding this supplement to your diet (but please let your doctor know about this) and who knows! However the study data show that for most people the addition of spirulina will only have a very mild impact on HBsAg.
@availlant I didnât mentioned that Iâm also on TDF, but as I know HBsAg decline on nucs is like 10x smaller, like 0.05 log per year thatâs why spiruline results looked not bad in compare to this but Iâm also concern that spiruline study may be sponsored by itâs producer.
so cccdna is responsible of production free HBsAg and hbv dna viral particles ? Or both produce both ?
HBsAg is released from infected cells in two ways:
As non infectious subviral particles (> 99.99% of HBsAg) from cccDNA but in larger part from integrated HBV DNA (which will not be affected by spirulina).
As infectious viral particles (< 0.01%) from cccDNA only (which appears to be mildly impacted by spirulina).
If only cccDNA is affected by spirulina we should not see any impact on HBsAg because cccDNA produces very small amount of viral particles in compare to subviral particles produced by hbv dna.
Im just trying to logically (or statistically) follow what youâv written it without deep knowlege of the topic
So remember that HBsAg comes mostly from SVP, not virus.
So mild inactivation of cccDNA will cause reduction in virus and SVP coming from cccDNA. This will lead to the mild overall reductions in HBsAg. The portion of SVP coming from integrated HBV DNA (which does not produce virus) will not be affected by cccDNA inactivation.
This is why the spirulina effect of HBsAg is so mild.
Hi availlant thanks for all the information you put on here I really appreciate that. I want to ask you a question. Does getting older play a big factor of maintaining this? I do eat properly and work out all the time and try to stay healthy as possible. Just trying to see if thereâs an outcome good or bad as we get older.
There is no good data examining the stability of functional cure in the elderly. However I am not aware of any reports of reactivation of HBV in this patient population either.
@availlant I admire how you dedicate your time to answer all questions in a very simple way for easy understanding. Thank you @ThomasTu for for giving everyone of us unequalled scientific and emotional support. If I remember vividly, we have a very active member here @Kinoti who developed HCC even though he has been on NUC, is it possible to consider him for NAPS compassionate use? His story is a very touching one. Iâm sorry if my request offends anyone.
Secondly, if someone has very low HBV DNA that current guideline says he wonât benefit from treatment but was placed on TDF by an inexperienced doctor, if the he/she stops taking TDF at any time, would the viral load skyrocket?
There is indeed a compassionate use program underway with REP 2139-Mg but it is only for qualified and experienced investigators (see here) and updated data on this program (including in patients with HCC) was recently presented at the APASL 2023 meeting (see here).
We take the very unfortunate progression of all patients like @Kinoti very seriously (and your suggestion is quite correct) but we have to focus the deployment of REP 2139-Mg in a way which accelerates its development so that hopefully all patients can have access as soon as possible.
Since current guidelines do not recommend NUC introduction with very low HBV DNA, we have very little data on how NUC exposure and then subsequent withdrawal would impact host control of infection in these kinds of patients. It seems reasonable to expect that NUCs will not negatively impact this immune control and so could be potentially removed without experiencing viral rebound. However we have to be cautious about this idea in the absence of any real data. HBsAg loss is still the gold standard for safely removing NUC therapy.
Recently updated Chinese guidelines now recommend treatment for any patient with detectable HBV DNA (see here - use google translate!) regardless of the presence of liver disease or not. This is a real breakthrough for patients and will hopefully give us data on how NUCs perform (especially in achieving HBsAg loss) in patients much earlier in the disease course and with much lower baseline HBV DNA than would normally be present at the start of NUC therapy.
do we have any data about the tools the body has to clear integrated HBV DNA or which immune cells detect this?i guess immune cells detect foreign hbvdna and trigger apoptosisâŚmaybe getting a fast turnover of liver cells pushing apoptosis, autophagy when hbvdna und or reinfection rates very low by ezetimibe or similar drugs may destabilize hbsag production and slowly fasten immune reconstitution towards hbv.of course this strategy only for very low hbsag, very low cccdna, hbvdna und.thank you
So we know that HBsAg loss and functional cure requires efficient inactivation of cccDNA and removal of liver cells containing integrated HBV DNA. The reason for this is that the production of HBsAg from integrated HBV DNA cannot be continually controlled by the innate immune response (as is the case for HBsAg coming from cccDNA).
Within the innate immune response, specific cells (we call these cells natural killer or NK cells) can move about detecting cells with the presence of a viral infection and remove them but they cannot specifically target HBsAg producing cells. For this we rely on HBsAg-specific white blood cells called T-lymphocytes (or T-cells for short) which are able to detect HBsAg producing cells and remove them from the liver. These HBsAg-specific T-cells are likely a critical aspect of the immune response required for functional cure and, not surprisingly, are almost entirely absent during chronic HBV infection because of the immuno-inhibitory properties of subviral particles (HBsAg).
Restoring the immune response to HBV very likely does increase the turnover of liver cells which is why flares of liver enzymes (ALT / AST) which signal the removal of infected cells are also observed during therapy ultimately resulting in functional cure.
The problem drugs like ezetimibe (and other statins) that they only have a minor impact on the production of subviral particles and the HBsAg clearance required to achieve functional cure (typically to levels < 1IU/mL) is an unlikely prospect when these drugs are used alone. This is why functional cure is easier to achieve with any therapy when HBsAg levels are low.
Hello @availlant, just a quick question please: Why are you running with Rep 2139-mg instead of Rep 2165? Is it because itâs safe enough and further along in the approvals or was 2165 not as good for some reason?
REP 2165 is a variant of REP 2139 which was designed to break down more rapidly and thus have significantly less liver accumulation than REP 2139. The details of these two compounds and their preclincal work-up can be found here.
In the REP 401 study, there was no difference in the antiviral activity against HBV with REP 2139-Mg versus REP 2165-Mg but the good pegIFN tolerability we had observed with REP 2139-Mg was poorer with REP 2165-Mg.
We had long known that NAPs have hepatoprotective properties and this study confirmed that these are linked to the liver accumulation of NAPs. Additionally, the greater stability of REP 2139 leads to greater intracellular recycling and nuclear accumulation which drives much better antiviral activity against HDV infection (the direct acting antiviral effects of NAPs against HDV occur in the nucleus) (see slide 5 here).
This enhanced liver accumulation is why REP 2139-Mg has much better antiviral activity against HDV and is also the reason why rapid reversal of ascites and normalization of ALT in cirrhotic patients before antiviral effects are observable occurs with REP 2139-Mg.
In short, REP 2139-Mg accumulation provides faster antiviral effects against HDV infection and a cushion for the liver during therapy, which is why it is so safe, even in decompensated cirrhosis.
I have never had antiviral treatment.
Yesterday, I had a hepatitis B test, and found that my ALT (191 U/L) and AST (134 U/L) values had significantly increased. Compared with the ALT (51 U/L) and AST (28 U/L) tests two months ago, they had increased by 3 to 5 times, but my HBsAg had decreased by 300 IU/ml (in fact, HBbsAg has been declining in the last year). Whether this is the bodyâs immune activation? I asked a chief physician and reminded him that my antigen had declined, He said that it is meaningless to see the fluctuation of HBsAg (I donât agree with him, and I doubt him a little). Every time, it is different. He asked me to start antiviral eating TAF and PegIF. My viral dose is the 7th power of 10, and HBsAg is currently 3700 IU/ml. So I want to ask you whether this situation may be immune activation, and whether PegIF can further help me reduce HBsAg. I hope you can give me some suggestions.
Productive ALT / AST elevations occurring during the natural history of HBV (in the absence of treatment) are typically associated with declines in HBV DNA and HBeAg seroconversion. With such a high viral titer, the ALT and AST increases you report are very likely a reflection of increased liver inflammation which is not productive. Your doctor is correct that you should really be taking antiviral therapy; these ALT / AST flares in the presence of high viral HBV DNA titers likely signal the beginning of liver disease.
Declines in HBsAg are only meaningful when HBsAg is much lower than your current levels and it is most likely that the decline in HBsAg you have experienced (with such a high viral titer) is simply a fluctuation. You should start TAF right away and if you attempt pegIFN, you do have a small but significant chance to achieve functional cure.
but Iâm also concern that spiruline study may be sponsored by itâs producer.