EASL 2013:SERUM HBSAG DECLINE IS FASTER THAN PREVIOUSLY ESTIMATED

[StephenCastlecrag]

Abstract 756

SERUM HBSAG DECLINE IS FASTER THAN PREVIOUSLY ESTIMATED IN LONG-TERM NUC RESPONDERS WITH LOW TREATMENT-INDUCED HBSAG LEVELS

G. Mangia1, P. Lampertico1*, F. Invernizzi1, F. Facchetti1, R. Soffredini1, G. Lunghi2, M. Colombo1
11st Division of Gastroenterology, 2Istituto di Medicina Preventiva, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy. *pietro.***@****

Serum HBsAg loss is the recommended stopping rule in NUC responders, yet this event occurs rarely. A 50% decline of HBsAg titers every 5 to 6 years has been described among HBeAg-negative NUC responders, leading to an estimated duration of treatment exceeding 30-50 years in most cases. Whether such a sloppy HBsAg kinetics applies also to patients with treatment-induced low HBsAg levels, is unknown.
Methods: 39 consecutive CHB patients displaying HBsAg titers between 100 and 10 IU/ml following long-term exposure to NUC, were recruited in a single center. HBeAg positive patients with a recent HBeAg seroconversion, immunocompromised patients, acute protracted cases and recently IFN treated patients were excluded. At baseline, age was 60 years, 87% males, 82% HBeAg-negative, 65% genotype D, 52% IL28B CC genotype, 59% cirrhotics, 97% with undetectable HBV-DNA, 95% with normal ALT, 67% NUC experienced, 36% on monotherapy (8 LAM, 4 ETV, 2 TDF), 64% on combo (LAM+ADV in 13, LAM+TDF in 12). Liver function tests, HBV-DNA and HBsAg levels (Abbott assay) were assessed every 3-4 months.
Results: During 39 (11-78) months of study, the median HBsAg titers progressively declined from 95 (range 16-270) IU/ml at baseline to 46 (0.02.-139) at year 1, to 23 (0.11-87) at year 2, to 7 (0.07-68) at year 3. The median decline was 50% every year, with more than 1 log decline over 3 years of continuous NUC therapy. The proportion of patients achieving >1 log decline increased over time, from 22% at year 1 and 2, to 37% at year 3 and 54% at last follow-up visit. Serum HBV-DNA remained undetectable in all patients, HBeAg seroconversion occurred in 3 patients between 5 and 10 months. Eleven patients (28%), 9 HBeAg negative, lost HBsAg between 11 and 73 months (median 27) and 10 of them successfully discontinued NUC.
Conclusion: HBsAg kinetics is faster than previously estimated in long-term NUC suppressed CHB patients achieving low HBsAg levels, a finding that might help in the design of cost effective algorithms of immunomodulatory add-on or switch therapies in NUC suppressed patients.


Assigned speakers:
Dr. Pietro Lampertico, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano , Milan , Italy

Assigned in sessions:
26.04.2013, 09:00-18:00, Poster Session, P02-07c, Category 07c: Viral Hepatitis B & D: Clinical (therapy, new compounds, resistance), Poster Area

[stef2011]

ignorance and stupidity

india has best price since roches lost patent there, exxura is roches made and should be around 95€ per injection

[aberdeen577]

Still no reply from my Dr on the request to have peg inf. Seems he just does not want to put me on this. Will look to get it in Indonesia or India.At qHBsAg 16.40 IU/ml it would be such a shame for me not to get rid of it. Just can't understand inaction of my doctor.

[andrey19]

no, there is hardly any info available on the net. I could not find anything on trials.

[stef2011]

the effect on hcv and hbv should be the same since it just boosts immune response, it is good to know itis in russia (i guess flights are cheaper, it is closer and prescriptions dont exsist in russia)

as to price still too expensive...

let's see if we find trials data, do you know links?

[andrey19]

Russian company BIOCAD got government approval and launches sales of peg interferon called Algeron in a couple of month. This new pegylated interferon is different from pegasys and according to producer is more potent. So far been tested only on hep c and reported results a very promising early virological response was achieved in 94% of patients against 88% with pegasys. ( http://algeron.ru/algeron/ ) No info on hbv yet but I think they will be testing soon. As for price they report at lest 30-40% less then pegasys. Pegasys price is $400 for injection.

Stef, studyforhope how do you think can algeron be more potent for hbv then pegasys?

[stef2011]

i mean the same product has prices so different that i dont thin it can be justified

yesterday i checked india prices and roches lost patent there in 2012, they are now producing under other names like exxsura which has prices as low as 95-100€ per injection.
peg is paid by healthcare in my country but if i had to pay it myself i d go to india to buy it, it is much cheaper even if i have to take flights several times to go there and buy it

[Magda123]

What do you mean when you say 'what a fraud'. You mean roche is not a good brand of preference?

[Magda123]

Yes roches..

[stef2011]

i got the post it is roches

what a fraud it is the same thing but.....
indonesia 150€ 195usd
italy         338€

[stef2011]

152€ per week wow that s a very good price and affordable to most...

what brand of peg was that?roches?

[Magda123]

Otan bought pegint in indonesia - 4 injections for USD780/-

[stef2011]

you may try it may have an effect with such low hbsag

[aberdeen577]

Thank you for this info. I will follow it up. Meanwhile should i try alinia along with tdf?

[stef2011]

definitly better try in vietnam or india....

[andrey19]

Pegasys 180 mg price in thai is 33 000 THB for one injection (around USD1150) and it has to be prescribed by doctor only. You can not get it in drugs store.

[stef2011]

you can use plain interferon alpha without peg because your status is very favourable to response, if intf price is very very low compared to pegintf better save money

intf needs 3 injections per week and pegintf one per week, they say peg is a little more potent but i dont see all this difference

[stef2011]

plain intf is off patent everywhere in the world but i guess they dont even sell it in US or europe while peginterferon is off patent in some asian countries and so you can find many brands and probably also the same brands here in europe but much lower price due to competition

as regards thailand i have no idea about patents and generics available we should post for info from other members

as regards buying at pharmacies you need prescription from a doctor and to travel back to UK

i have been told to go on "a quarter of peg inf -pegasys 180 mg weekly for 3 months". Do i need to mention this when i buy?

of course there may be lower doses available so best to menthion the dose, i guess the doctor will

can i purchase 3 or 6 months supply at one time?
yes but you need a temperature controlled bag, interferon needs refrigeration at about 4° i guess

[aberdeen577]

Stef, i go to thailand several times a year for work and my questions are
can i buy peg inf there?
you mention generic, whilst I know the word meaning i am unsure of context. Does it mean off patent
i have been told to go on "a quarter of peg inf -pegasys 180 mg weekly for 3 months". Do i need to mention this when i buy?
And finally, can i purchase 3 or 6 months supply at one time?

[stef2011]

if india, vietnam are available to you there treatments are very cheap and pegintf is available generic too, also there are some very good doctors who cured members of medhelp

[aberdeen577]

Thank you so very much Stef. U will look into this. You are a great advisor to so many people in this forum and you probably don't realise it. You make our lives easier for us.

[stef2011]

http://clinicaltrials.gov/ct2/show/NCT01821794?term=tenofovir+peginterferon&rank=4

http://clinicaltrials.gov/ct2/show/NCT01373684?term=tenofovir+peginterferon&rank=9

http://clinicaltrials.gov/ct2/show/NCT01706575?term=tenofovir+peginterferon&rank=10

[stef2011]

http://clinicaltrials.gov/ct2/show/NCT01821794?term=tenofovir+peginterferon&rank=4

http://clinicaltrials.gov/ct2/show/NCT01373684?term=tenofovir+peginterferon&rank=9

http://clinicaltrials.gov/ct2/show/NCT01706575?term=tenofovir+peginterferon&rank=10

[stef2011]

no worry about these small numbers but of course the time to clear hbsag by simple tdf can be very very long it doesn t worth to waste such an opportunity like yours

What can i do?
go to another doctor more expert, or move to italy possibly pisa for the combo intf plus tdf, by the way there are trials recruting, so free of any charge, although dont know if they accept so low hbsag

or go to pisa have prescription and go buy intf yourself if UK healthcare doesn t cover that.dont know about uk but you may inquire vatican city pharmacy or swiss pharmacies, pegintf is very expensive though

the best chance is get in the trial, it is made for those under long term tdf with hbvdna und, i think they require about 3 years of tdf and dont know about hbsag level if they accept the very low ones because it is of course a 100% clearance result

[aberdeen577]

Hi Stef,
and thank you. You did say last time that i would clear. Now i have gone up to over 16Iu/ml i am worried it will continue thus trend upwards and finally put ne out of reach of clearance by inf. My consultant does not seem that bothered. He knows my s is very low but still dies not offer me peg inf. What can i do?. Can i buy it elsewhere, how much would it cost me? Please help to see if i can get it anywhere.