poster of etv+tnf

[stef2011]

http://www.natap.org/2011/AASLD/AASLD_34.htm

i like 3 points of this presentation:
overall hbvdna suppression about 1log more on etv+tnf
overall hbsag loss and hbsg seroconversion superior on etv+tnf

the bad points about this study:
no hbsag quant report
no cccdna report

without theese last importnat parameters i think this study is almost useless, the point of combo is no resistance very long term and more hbsag cccdna suppression
we can only guess that both hbsag nad cccdna are more suppressed on combo since we have more hbvdna suppression and more hbsag loss

[stef2011]

another thing i would like to compare is tnf+etv and tnf monotherapy since tnf is more  potent than etv i d like to see if there additional cccdna/hbsag suppression since sides are irrelevant if not less on the combo for creatinine changes

[StephenCastlecrag]

overall hbvdna suppression about 1log more on etv+tnf
overall hbsag loss and hbsg seroconversion superior on etv+tnf

I don't see them from the slides???

[stef2011]

sorry my mistake only 0.4log more at 48weeks and 0.1log more at 96weeks but you cant see this really from meaure in blood because this depends to the level of hbvdna in patients, you can see the maximum suppression here.i hope they will measure total hbvdna in the liver and cccdna, there you can see if there is a difference and for longer than 96weeks

from hbsag loss % patients

[StephenCastlecrag]

I don't know why HBV combination therapies don't do as well as expected. I agree with you that they should measure the HbsAg quantities. I imagine measuring total hbvdna and cccdna require biopsies and will be costly.

[4est]

how is behavior of HBsAg quantity under different antivirals option?
will this going down?

- I remember that @ studyforhope explain that under antivirals cccDNA decrease until 10 times (if I remember correct), so this is also apply to  qHBsAg ?

[April63]

I'd say the data is somewhat disappointing, don't you think?

[StephenCastlecrag]

I can only remember studyforhope mentioning that antivirals do reduce HbsAg, but I can't recall the reasons why. Maybe antivirals restrict the pool of cccDNA inside an infected liver cell from being refilled?

Serum HbsAg comes from 3 sources:
1. cccDNA -> HbsAg particles
2. cccDNA -> new virions with HBsAg coat
3. HBsAg gene embeded in our human genome->HBsAg (not idea in what form)

Just my own understanding.

[stef2011]

the problem by the measure of hbvdna in serum is that patients have a fixed quantity in serum of hbvdna and once it gets negative there is no way to measure the effect of single antivirals or combos, while cccdna and total intrahepatic hbvdna are still detactable and you can still measure that, hbsag is another good measure as well, so i dont see any point in what they published
alt and virological results are also useless, these nucs have no direct effect on these

a big limit is also 96 weeks, too short but anyway once a combo is started you can t go mono, it is not safe, so i hope they will keep registering results years by year and the centers with ccdna data should also make it available

we have just one study i posted a lot of time ago on combos with hbsag reduction:
etv or etv+tnf were the most potent with hbsag resuction of about 8-10% per month, they did not say if hbeag pos or neg, i think it is mixed and then just joint data
all other combos of nucs or mono therapies were almost useless with reductions like 2-3% per month

anyway i think that only cccdna and hbvdna intrehepatic can be a good measure of combo results