efficacy of two-step peginterferon and etv combo, hbsag clear 30% vs 0%

[stef2011]

http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2893.2011.01469.x/pdf

At week 96, five patients of Group 1 plus Group 2
reporting HBsAg loss reached 21.7% (5/23) by two-step
Pegasys treatment, and three more patients had low titre of
HBsAg (<5 IU/mL) and low HBV DNA levels (<1000 copies/
mL) with ALT normalization.
Efficacy of two-step Pegasys treatment in HBeAg-positive
vs HBeAg-negative CHB
For comparison of the efficacy of two-step Pegasys treatment
between Group 1 (HBeAg positive) and Group 2 (HBeAg
negative), the rates of HBsAg clearance and seroconversion
at week 96 were 15.4% (2/13) and 7.7% (1/13) for HBeAgpositive patients; 30% (3/10) and 20% (2/10) for HBeAgnegative patients. The rates of undetectable HBV DNA were
30.8% (4/13) and 30% (3/10, P = 0.968); SVR were 69.2%
(9/13) and 80% (8/10, P = 0.56) for HBeAg-positive and
HBeAg-negative patients, respectively, at week 96. No significant difference was observed (Fig. S1)

[stef2011]

http://hub.hku.hk/bitstream/10722/56989/1/FullText.pdf?accept=1

again got no time now but will read together

my point is, and not only mine, even dr brunetto said we miss immunological markers in hbv infection..., is see what type of markers can we use to see if our immune system gets activated in fighting hbv

i hope the decrease of hbsag can be useful to see if gcmaf has any effect but i am also thinking tht when immune system is activated hbsag gets down in about 2-4 weeks only.so it may be better to have more sensitive markers that allows to see any immunological improvment much earlier than final immuen activation and hbsag clearance

[stef2011]

found new articles about immune effectors of hbsag clearance.i havent read them yet, i will later tonight, just had a look on first link and it is very interesting, i think that we need the effects of gcmaf on cd4 and nk cells and maybe after this boost try a combo interferon+nucs and etc f there is some boost on cd4,cd8, nk cells and of course normal nagalase

http://www.pnas.org/content/107/2/798.full

it is also good to know that steam cells therapies are being dicussed in kiev by most international experts for direct therapy, not just qua qua

i remember a post about it, do you remember the good effects of steam cells?was it about the fact steam cells cant be infected by hbv?

[PinoyHBVDNA]

U mean hbv invades the bone marrow 1st before the liver? If that's the case how early does it invade the marrow? I am confused.

[stef2011]

there are only ipotesis on the dentric cells and macrophages non response, we know hbv infects bone marrows before infecting the liver for some weeks and we also know hbv uses macrophages to get to the liver

we know that hbv, like all viruses and bacteria, uses nagalase to inactivate macrophages, onc macrophages are inactivated there is no way to let the immune system know hbv is there because also dentric cells are inactivated
nagalase is used by viruses to enter the cells and to inactivate immune system.i guess that once we see results of gcmaf on me we may confirm this ipotesis.

what we really dont know is how dentric cells are inactivated, if it is because the excess of antigens orother ways

interferon gamma and tgf beta are one of the cytokines stopping hbv replication without liver damage.interferon gamma is low on all cronic carriers

[StephenCastlecrag]

Thanks, Stef2011. You are right - lowering hbvdna must be due to either our immune system and/or the virus itself (mutation).  I read:

NK (Natural Killer) cells recognise changes on the surface of infected cells and kill these cells.
CTL (Cytotoxic T cells) recognise antigens on the surface of the infected cells and kill these cells.

Now,  CTL cells recognise peptides displayed by MHC Type I molecules on the surface of a cell. I understand all cells with nucleus constantly display fragments of proteins (peptides) inside the cells using MHC Type I molecules.

I have no idea how NK cells recognise an infected cell.

So basically, I am trying to understand what regulate the amount of CTL? Does lower hbvdna make a cell less recognisable by NK cells and CTL?

Of course, there is also the question: can immune system stops viral protein expression by various cytokines, such as Interferon alpha and gamma? No killing no rise in ALT.

Now, I will go and read your article about NK cells and Interferon gamma.

Cheers.

[stef2011]

the bad thing is not only PN itself but the fact the the drug industry is not interested in lowering hbsag, and everytime they find something no big trials or studies are supported, i think the excuse of PN will definitely stop any study on this