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]

remember there is a combo which lowers hbsag very fast, 1log in 24 weeks, interferon+telbivudine

the problem is interferon increases peripheral neurophaty which is a telbivudine side effect, so very close monitoring and way to prevent peripheral neuropathy should be applied.
a staggered thereapy interferon+telbivudine is a good option but a researcher/expert on PN is needed to understnd why it develops and how to prevent it

[April9903]

Very interesting discussion. I will discuss with my doctor on treatment options. To be honest, I am scared to start tx.

[stef2011]

Our findings raise the possibility of immunotherapeutic targeting of IL-10 and TGF-β in CHB, with the caveat that these cytokines govern a critical balance between impeding pathogen clearance and restraining immunopathology.

both IL-10 and TGF-β are available at redlabs
http://www.redlabs.be/documents/Request%20Form%2008-10IMMUen.pdf

of course tests like these have a meaning only on experimental immune therapies like gcmaf, on normal interferon hbsag quant and hbvdna will guide therapy response, while on nucs all immune tests are almost useless since they sometimes suppress immune response or sometimes restore it only partially

[stef2011]

very interesting part of the study:

IL-10 is induced in CHB and recapitulates the NK cell defect in IFN-γ production

Effector function of NK cells is tightly regulated by the cytokine milieu and their production of IFN-γ can be inhibited by immunosuppressive cytokines such as IL-10[12], [16] and IL-17[13]. The levels of IL-17A were not elevated in sera from patients with CHB compared to controls (Fig3a). In contrast, circulating concentrations of IL-10 were significantly increased in patients with active HBV disease (Fig3b,c by CBA, confirmed by ELISA, data not shown), correlating with viral load (r = 0.48, p = 0.002) and ALT (r = 0.37, p = 0.03). IL-10 levels showed a trend to decrease on antiviral treatment but remained significantly higher than in controls (Fig3c), consistent with the limited restoration of NK cell IFN-γ production in these patients.
To test whether IL-10 could induce the defect in NK cell IFN-γ production seen in CHB, we re-assessed NK cell effector function with or without the addition of exogenous IL-10. IL-10 significantly suppressed NK-cell derived IFN-γ (Fig3d), particularly in those patients in whom it was not already substantially reduced (Fig3e, and in healthy controls, data not shown). By contrast, IL-10 had no effect on cytolytic ability or TRAIL phenotype (Fig3f) and did not affect the percent of NK cells (FigS3a). The ability of IFN-α to further induce NK cell TRAIL expression in vitro[4] was also not abrogated by IL-10 (data not shown). The effect of IL-10 was consistent but more modest on purified NK cells (FigS3b), suggesting that some of its suppressive activity on NK cells is mediated indirectly via other constituents such as APCs. The contrasting effects of IL-10 on TRAIL and IFN-γ expression represented differential regulation of these effector functions in the same NK cells rather than the emergence of two distinct subsets. The small population of TRAIL-expressing NK cells present in healthy donors were at least as able to produce IFN-γ as the rest of the NK cell population (FigS3c). The addition of exogenous IL-10 suppressed IFN-γ in NK cells regardless of their TRAIL expression (FigS3c). In line with this, gating on the expanded population of TRAIL-expressing NK cells found in CHB demonstrated that their IFN-γ-producing capacity was no more reduced than that of the non-TRAIL-expressing fraction (FigS3d).

[stef2011]

i had cd counts at about 6 weeks full dose gcmaf, all cd counts were different than those observed on serum hbv cronic carriers.
if i can get a measure of interferon gamma and cytokines we can get an iades if all those counts are high for hbv or for other pathogens.

the ebest test would be cd isotopes towwards hbv in the liver but this test cant be obtained due to highly research type of test and biopsy requirement, but hbsag count, cd counts serum and cytokines should help get an idea of what gcmaf is boosting and of course nagalase return to normal levels

[stef2011]

http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1001227

this study shows one of the ways imune system can keep hbvdna low with normal alt.this is by nk cells secreting interferon gamma