Add -on interferon to a stable nucleoside, hbsag loss 40% full poster

[stef2011]

https://docs.google.com/open?id=0B_yFgxI8KNcROTI2YzFkYTctMjZjMy00MjBjLWE0ZDEtNWY3NmI0MDQ3MzNl

this is very important because we can make the following comments:

adefovir had the higest results but since tenofovir is similar with less toxicity, more potency and no resistance we maight have same or higher results

another observation is etv mono for only 3 years and huge hbsag decrease from 7900iu/ml.while all others had already very low levels of hbsag this patient had response on the hbsag range where interferon mono has little decrease on hbsag.the decrease looks also a sudden decrease and not slow and homogeneous

too bad we dont have etv+tdf combo among these patients i guess it may have stronger effect

[4est]

and another clinical trial that have to keep an eye on it:

http://clinicaltrials.gov/ct2/show/NCT00877760?cond=Hepatitis+B&cntry1=EU%3ARO&rank=3

[4est]

A new trial for tnf + inf  is in recruitment phase:

http://clinicaltrials.gov/ct2/show/study/NCT01277601?term=hepatitis+b&recr=Open&cntry1=EU%3ARO&rank=1&show_locs=Y#locn

this is a trial that we have to look for the results.

[stef2011]

http://www.kenes.com/easl2010/orals/118.htm
this was peg+telbivudine (ltd) 24-48weeks with hbsag 0.5log decline on 63%

Background and aims: HBeAg seroconversion is a key milestone for HBeAg-positive chronic hepatitis B (CHB) patients allowing for treatment discontinuation. Compared with other treatments, higher rates of HBeAg seroconversion (e-seroconversion) are reported with PegIFN or LDT. We aimed to investigate whether PegIFN+LDT combination could further improve antiviral efficacy and e-seroconversion compared to their monotherapy.
Methods: 159 HBeAg-positive CHB patients were randomized (55 LDT, 54 PegIFN, 50 PegIFN+LDT). 110 patients (49 LDT, 43 PegIFN, 18 PegIFN+LDT) reached treatment week 24 (W24), but the study was terminated early due to PN events with PegIFN+LDT. Key efficacy (HBV DNA, ALT, HBsAg/HBeAg quantitation by Abbott Architect) and safety is reported.
Results: Mean baseline HBV DNA levels (log10copies/mL) were 9.8 (LDT), 9.6 (PegIFN), 10.1 (PegIFN+LDT). At W24, LDT containing regimens achieved significantly greater viral load decline than PegIFN (figure 1).
HBV DNA became undetectable in 35%, 7% and 71% of patients (LDT, PegIFN and PegIFN+LDT, respectively), p0.5log10IU/mL) occurred in 41% LDT, 31% PegIFN and 63% PegIFN+LDT treated patients (p=0.03); ALT normalization: 54% LDT, 32% PegIFN, 12% PegIFN+LDT. For the few LDT and PegIFN patients who achieved W48, 7/19 and 3/12 respectively had e-seroconversion.
ITT discontinuations due to SAE/AE occurred in 7.3%, (LDT), 5.6% (PegIFN) and 18%, (PegIFN+LDT). PN cases with PegIFN+LDT were more severe and shorter median time (months) to symptom (4.5, range 2-6) vs LDT (14, range 4-25). 9 SAE PN cases were drug related, 8 were on PegIFN+LDT, 1 was on LDT and at last follow up, 6 were improving, 2 ongoing and 1 unknown.
Conclusions: The combination of PegIFN+LDT provided very potent antiviral efficacy with rapid and profound reduction in HBV DNA and HBsAg/HBeAg levels, but combination therapy with PegIFN+LDT carried an increased risk of PN. The underlying mechanism needs further investigation. Despite increased efficacy, concomitant use of PegIFN+LDT should be avoided at present.

[4est]

http://www.medhelp.org/posts/Hepatitis-B/wow-found-post-of-a-guy-who-cleared-after-48weeks-combo-interferontelbivudine-in-italy/show/1643426

just to keep all information in the same place :)

[stef2011]

thank you very much for finding the emails but i have just returned from pisa and they know already that hbv is cleared by combo int+tdf or int+etv, just a matter of time to clear almost all of hbsag.

so now we just need to make these combos and see how hbsag goes down and personalize interferon+nucs durability according to it:

for example interferon+tdf or etv doesn t lower hbsag by 24 weeks, stop interferon and continue the antiviral only.interferon can be retried later on

if hbsag keeps lowering the combo must be kept as long as hbsag detactable, even 2-3 or more years

[4est]

http://www.medhelp.org/posts/Hepatitis-B/news-from-researchers-interferontdf-or-etv-clears-hbv-in-almost-all-patients-96weeks/show/1643024

to have tractability for all related topics