HEPDART 2001 - abstract data

[4est]

http://www.informedhorizons.com/hepdart2011/pdf/FinalProgram&Abstract%20Book_HEPDART2011.pdf

[StephenCastlecrag]

Excellent resources, thanks.

[4est]

http://www.ihlpress.com/gaj_hepdart2011.html

selected slides form 2011 hepdard

[StephenCastlecrag]

(REP 9AC'). REP 9AC was modified to reduce proinflammatory
activity(side effects  consistently observed during drug
administration of REP9AC). and improve compound
stability. Early interim data from seven new HBV
patients treated with REP 9AC’ show effective
clearance or substantial HBsAg reductions in all
patients in the first 10 weeks of treatment. Three
of these patients have already experienced a 3-4 log
decline in their HBV DNA. No pro-inflammatory side
effects have been observed to date with REP 9AC’
administration.

[OrientS]

Good summary ..

what happened for those new 7 patients treated by REP9AC?
less inflammation!
the inflammation occured after treatment or before?

do they get rid of the virus?

what is the effeicency of the REP9AC on the trial paients?

[stef2011]

you are correct etv cant be used if there was lam use because there is no way to know if lam resistance has developped
all tests cannot detect mutants 100% except ultra deep sequence

from deep sequence it also come out that my mutation q215S can make lam resistance if lam is used.research was not made on use of adv and etv with q215S but the same thing happened with lam may happen on etv...in the end only tenofovir looks like safe 100% on resistance

[4est]

one warning, if I remember  correct, regrading the usage on Ent on the patients that used Lam in past - even if they are not develop Lam resistance.

[StephenCastlecrag]

News from HEPDART 2011, my opinions:

- REP9AC - 7 new patients tried the new REP9AC', less inflammation and seem to be just as effective. Need to observe longer.
- Nitzaxonide (Alinia) - in the case of HBV, seems to act by interfering with the HBcAg phosphorylation needed for nucleocapid stability, thereby inhibiting virus replication. This seems to be different to the research mentioned by 4est above. No plan for clinical trial yet.
- Interferon Lambda - in HCV clinical trials, seem to be effective and cause less side effects. Need to ask Stef2011 about its use in HBV.

any other news that raise the hope ..ALL EARLY STAGES
1.GS 9620, a TLR7 agonist
2. A HBV capsid inhibitor
3. Programmed death receptor-1 as a novel immunotherapeutic strategy
4.Another potential therapeutic vaccine (seems to be the old Hepavaxx)

[4est]

regarding alinia discussion below is a 2009 link that can bring more info:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2670405/

[OrientS]

As you active member and cooperative here ..

can you highlight more on the results of HEPDART 2011, specially that related to:
- REP9AC
- Nitzaxonide (Alinia) ... unfortuanately it is not available in Saudi Arabia
- Interferon Lambda

any other news that raise the hope ..

Thanks ..

[StephenCastlecrag]

Thanks for the reference. It makes sense that the T-cells responses are inadequate in the case of chronic hbvers. CD4+ & CD8+ T cells specific for as many antigens, such as Core, E, and S, are necessary for clearance of HBV.

[stef2011]

cronic carriers have all the antibodies hbsab, hcab, hbeab the problem is they are all in low quantity and virus can make more antigens by the infected liver cells than immune system can, so hbsab is neutralized by hbsag immediately

the quantity of hbcab igg and igm is extremely low on cronic carriers to be useless

it is difficult to find the study i read long time ago, anyway there are many other reporting about the same.ferrari study was good because he published the quantitative measure of all antibodies.lately we have also an assay to measure hbcrag because when it gets undetactable the overall infection of hbv improves and cccdna lowers

http://www.mendeley.com/research/cellular-immune-response-hepatitis-b-virusencoded-antigens-acute-chronic-hepatitis-b-virus-infection/

Abstract

The proliferative response of PBMC to hepatitis B virus (HBV) envelope, core, and e Ag was analyzed prospectively in 21 patients with acute self-limited HBV infection and compared with the response of patients with chronic HBV infection and different levels of HBV replication (i.e., hepatitis e Ag (HBeAg)- or anti-HBe-positive) and liver damage (i.e., chronic active hepatitis or chronic asymptomatic carriers). Our results indicate that: 1) HBV-infected subjects who develop a self-limited acute hepatitis show a vigorous PBMC response to hepatitis B core Ag and HBeAg, as expression of T cell activation; 2) appearance of a detectable lymphocyte response to HBV nucleocapsid Ag is temporally associated with the clearance of HBV envelope Ag; 3) in patients with chronic HBV infection the level of T cell responsiveness to hepatitis B core Ag and to HBeAg is significantly lower than that observed during acute infection; 4) T cell sensitization to HBV envelope Ag in acute and chronic HBV infection is usually undetectable and when measurable is expressed transiently and at low levels. These results may reflect immune events of pathogenetic relevance with respect to evolution of disease and viral clearance.

[StephenCastlecrag]

I still don't understand. Surface antibodies can attach to the Surface antigen, the coat of the virion, therefore preventing infection. That is why Surface antigen is used in vaccine to elicit the production of Surface antibodies. But what can the Core antibodies do? It just cannot see the Core antigen. All chronic hbvers have the Core antibodies.
A strong HBcAb response may just be am indication of a strong immune response, but I still like to know what the Core antibodies can do to help clear the virus, both inside and outside the liver cells.

[stef2011]

it is the opposite hbsag is needed to protect the core and neutralize immune response against virions
i ll need to look for the study of hbv immunity by ferrari univeristy of parma, he has foucsed his studies on immunology of hbv
he measured all immune responses and the main difference between cronic and acute was the hbcab which is almost undetactable/low in cronic

also hbv vaccine is very weak to make strong immunity because it uses hbsag instead hbcag, the new vaccines are made by hbsag+hbcag and are much more potent.current hbv vaccine is not able to block hepatitis 100% although it can avoid cronic hbv and has the problem of 5% non responder, this new vaccine has resolved these issues

hbsab blocks liver cells reinfection but the clearance of virions is made by hbcab.hbeab is the less important hbv canbe cleared even with no hbeab and this happens in both acute and cronic hbv

[StephenCastlecrag]

You have to explain to me why HBcAb is useful against the HBV virus? I always thought HBcAb is useless because the virion is coated by the Surface antigen and the core antibodies just cannot see the core antigen.

[stef2011]

if you are not aware of immune studies by ferrari and other scientists, hbv is cleared by a strong hbcab response which is very low/und on cronic patients.so the fact that alinia is active on hbcag is very very interesting

also hbcab igg and igm quantitative can be very interesting on cronic patients but very few check these antibodies because they are always extremely low on cronic hbv.the clearance of cronic hbv happens by a high increase of hbcab which allows also hbsab to come detactable

i havent yet chacked interfern lambda, i forgot to ask about it in pisa, i d like to see data on its effect on hbsag quant i hope some data on human trials will come out soon

[StephenCastlecrag]

Thanks 4est. Read all about

1. The new REP9AC'
2. Nitazoxanide (aka Alinia)
3. Lambda Interferon (another stef2011 favourite)

and many more.....