72wks IFN EAG+

[grmr]

HI guys, are there any studies / trials proving the efficacy of 72 wks mono-ifn on EAG+ patients?

I'm now at week 48, still EAG+  (no hbs decrease at all since the beginning)  and wondering if 72 wks would be beneficial

Thx

[grmr]

thank study for yuor input.. wondernign what results could be on eAG+ carriers..

[studyforhope]

Here is a study that used 60 weeks of pegIFN. Note the low criteria for "SVR" at followup..Less than 20000 copies of HBV DNA...

Am J Gastroenterol. 2007 Dec;102(12):2718-23. Epub 2007 Jul 27.
A pilot study of extended duration peginterferon alfa-2a for patients with hepatitis B e antigen-negative chronic hepatitis B.
Gish RG, Lau DT, Schmid P, Perrillo R.
SourceDivision of Hepatology and Complex Gastroenterology, California Pacific Medical Center, San Francisco, California, USA.

Abstract
OBJECTIVES: Forty-eight weeks of peginterferon alfa-2a is the approved regimen for chronic hepatitis B (CHB). Standard interferon is more effective for hepatitis B e antigen (HBeAg)-negative CHB when given for longer than 1 yr. This study evaluated peginterferon alfa-2a for 60 wk, alone or in combination with lamivudine.

METHODS: Thirteen patients with HBeAg-negative CHB received peginterferon alfa-2a (180 microg/week) for 60 wk or peginterferon alfa-2a (180 microg/week) for 12 wk followed by 48 wk of peginterferon alfa-2a plus lamivudine. The primary end point, sustained virologic response (SVR), was defined as a reduction in hepatitis B virus deoxyribonucleic acid (HBV DNA) of >or=2 log10 copies/mL and HBV DNA90% decrease in HBsAg concentration at week 60, including 3 with undetectable HBV DNA at week 84 and a fourth who met criteria for SVR.

CONCLUSIONS: Sixty weeks of peginterferon alfa-2a with or without lamivudine resulted in a higher rate of SVR compared to historical controls with HBeAg-negative CHB treated with 48 wk of pegylated interferon. Larger studies are necessary to assess if longer duration therapy is more effective than the standard regimen and results in a greater decline in HBsAg concentration.

[stef2011]

a flare is good only when getting hbsag to very low less than 1000iu/ml on genotype d

[stef2011]

no that s not correlated with flares, these mutants are present in hbeag positive too but much less than hbeag negative

i dont know why some are wild type on both hbeag pos and hbeag negative and others bcp/precore positive on both hbeag pos and neg

despite bcp/precore positivity you can be inactive with very low hbsag too, i guess it is a balance between immune system and virus in the end

[grmr]

thx stef.. so  does hbeag becomesnegatve without mutation when a severe flare happen? and therefore hbeag becomes negative with no falre this means virus mutation..right?

[stef2011]

too many variables it can be different from person to person

if you make tests baseline and no bcp precore and hbeag pos you can be sure not to develop these mutations under treatment

[andrey19]

If one was diagnosed with hbeag neg hep b. He is considered to have virus for long time. How long does it usually take to become hbe neg off therapy since virus got into ones blood?

[stef2011]

becoming hbeag neg off therapy is worsening and not imrpving wth our genotype D

hbeag will change before 30yo for sure but this wont be an imrovment for you, the key is getting hbeag neg without the mutations and keep hbv in check for a long time

my sister is also not suggested any therapy since fibrosis is zero, we have probably less corrupted doctors in italy so antivirals are actually prescribed only when needed, that s too say damaged liver or older age

[calebz]

Just curious what is your Fibroscan result ? Or better post your other results.
I was hbeag negative around march 2012 and i became positive in Nov 2012.

[grmr]

yes you got the point stef..i'm trying to realize what is really worth for the liver as my fibrosys is F0 almost...

anyhow i still struggle to understand if one can be eag +ve all life lonf or sooner or later (even if with falres/liver damages) eag -ve is the natural outcome of chornic hbv..

i know there're several metohd to keep und dna for years but at my age 27yo it does not seem to be the best solution as we do not know so far which sides tdf/etv may have after 30/40 years of 1 day pill...

do appreaciate your posts and valuabel inputs.

[stef2011]

i also understand he is tired of treating hbv, he has no liver damage so he actually need no therapy and can go on waiting for a real cure with little danager at his age

[stef2011]

i think he can keep intf for sometime, maybe try adding ezetimibe for 1-3months to see if any effect and then stop or go for long tenofovir treatment to recover immune response to hbv

irrispective of hbeag tenofovir mono for 3-5 years should be able to recover some immunity and at that point intf might work like for others

the bad point of all this, there is lways a percentage of no response whatever we try, in the sequential treatment failure was 10%, a patient on lam+adv

[StephenCastlecrag]

Ok. Your method is based on Stef2011's recommendation. It's aim is for a complete cure. The NICE guideline and others are aimed at controlling the virus - keeping ALT normal and hbvdna as low as possible.

[grmr]

that's curiuos because i read the opposite.. namely nucs and then stop nucs and go on ifn.... that's what i did basically i had combo tdf+ifn for 11 months and now on ifn mono..

[StephenCastlecrag]

I think you are missing the point of the draft. You already had 48 weeks of PegIFN with no HBeAg seroconversion, so according to the draft, you should stop PegIFN, then continue with Tenofovir/Entecavir(1.5.17, 1.5.18) unitil HBeAg seroconversion, then can consider stopping Tenofovir/Entecavir 12 months after HBeAg seroconversion(1.5.20).

[grmr]

do not know how long this "tail" is... thx for the draft but i do not think it'd be effordable to me.. anyhow this is the 2nd ifn course I do... the first one was stopped 6month after start as not responding..

[StephenCastlecrag]

There are trials of using PegIFN beyond 48 weeks to 96 weeks. I forgot the details. You will often find HBeAg seroconversion after stopping PegIFN as the tail of benefit of Interferon seems to be long.
I copied below the DRAFT NICE guideline from England. It recommends 48 week of PEGIFN as the first treatment for all HBeAg+ve patients, followed by Tenofovir/Entecavir if no HBeAg seroconversion.
Please bear in mind, it is a draft and is in the open discussion phase.

Treatment sequence in adults with HBeAg-positive chronic hepatitis B and compensated liver disease
1.5.15 Offer a 48-week course of peginterferon alfa-2a as first-line  treatment in adults with HBeAg-positive chronic hepatitis B and  compensated liver disease.
1.5.16 Stop peginterferon alfa-2a 12 weeks after starting treatment if HBV  DNA level has decreased by less than 2 log10 IU/ml and offer second-line treatment in line with recommendations 1.5.17 and 1.5.18.
1.5.17 Offer tenofovir disoproxil as second-line treatment to people who do not undergo HBeAg seroconversion after first-line treatment with peginterferon alfa-2a.
1.5.18 Offer entecavir as an alternative second-line treatment to people who cannot tolerate tenofovir disoproxil or if it is contraindicated.
1.5.19 In people taking tenofovir disoproxil who have detectable HBV DNA at 48 weeks of treatment and no history of lamivudine resistance, consider adding lamivudine to tenofovir disoproxil. In people with a history of lamivudine resistance, consider adding entecavir to tenofovir disoproxil.
1.5.20 Consider stopping nucleoside or nucleotide analogue treatment 12 months after HBeAg seroconversion in people without cirrhosis.
1.5.21 Do not stop nucleoside or nucleotide analogue treatment 12 months after HBeAg seroconversion in people with cirrhosis.

[grmr]

hi stef, i believe i'll quit ifn in 6/7 wks so i'll have done a total of 60wks with no hbs decrease nor eag seroconversion.. still EAG+ and DNA UND..

what then should i do if ALT flares up again??

[stef2011]

http://www.medhelp.org/posts/Hepatitis-B/Interesting-strategy/show/1881242

maybe you missed this post about the staggered intf/nucs strategy to get very high hbe and hbs seroconversions, i d go for this if intf fails.try to check if your doctors are aware of this strategy, in pisa they do since 2009