Entecavir + Interferon combo

[cyrus131]

Dear all,

     I have been on Entecavir 0.5mg for over 6 years and my HBV DNA is nearly undetectable.  I will see my doctor tomorrow and what tests should I perform so as to assess whether I will benefit from the Entecavir + Interferon combo treatment (i.e. higher chance to achieve Hbsag seroconversion.)  Many thanks.

Regards,

Cyrus

[studyforhope]

aldara on the skin where you inject the vaccine is a very promising approach, and very available. The injections should be done intradermally, maybe 6 to eight injections spaced about 1cm on skin that has been prepared with aldara 2 hours before and again immediately before the injection. the doses for intradermal vaccinations are less than for intramuscular. having zadaxin in the mix would enhance it further, a Canadian trial has proven that.

Strong data support the notion that at a very low hbsag Zadaxin can induce a more permanent seroconversion than peg ifn.
it is unclear if antivirals at this time are helpful or harmful for the final effect. I have seen a paper where the group with antivirals did much worse than the one without it at this stage. Maybe the slightly enhanced virion production at this low stage gives incentives to immune processes.
Vit D is beneficial at all these approaches. It is unclear if very high doses improve the situation further over just high doses.

[stef2011]

is zadaxin the best drug once we reach very low hbsag and some detectable hbsab?
or this combo might have more chances pegintf+ydf or etv+zadaxin+vit d3+hbv vaccine with aldara on skin where we inject vaccine?

thanks

[studyforhope]

You might have a very low titre just above the threshold. It is not of major functional importance at this point. But the Tcell stimulation with Thymosin alpha/Zadaxin will likely get your Ab titre substantially up. Even then that is just mostly a good marker of improved Bcell function, but what matters will be the increased Tcell stimulation that will tend to attack and decrease remnant infected cells, a process that you cannot easily see or measure, but it will result in a neg surface antigen. there is also a factor of luck involved here, epitopes and matching Tcell clones  must be available for stimulation or might occur de novo.

[cyrus131]

Dear studyforhope,

Do you need I still have detectable Anti-HBs?


Cyrus

[studyforhope]

It's unclear if this will stay low or slowly return to higher values even if Entecavir is continued. In my opinion,if you want to stabilize or seroconvert the hbsag zadaxin for about 6 month is the most promising option, better than peg ifn. You would see success also in clearly increasing anti hbs titers. It should be easy to find a doc in hong kong who will prescribe zadaxin to you.

[stef2011]

continue peginterferon+etv plus vitamin d3 10.000iu daily

maybe try adding also simvastatin, hbv vaccine and zadaxin

i d say this is not a clear relapse, i guess immune system is still working on it but it is best to chose immediately what to do and pegintf is for sure the best choice to consolidate clearance

[melcul]

From my non expert advice, you are very lucky, definetly going to clear hbsag, but you need vaccine i guess and some treatment! That is a very very low quantity  Wait for the expert opinion  of our experienced friends here , stef and study

[cyrus131]

Dear studyforhope and Stefano,

Just got my quantitative HBsAg result : 0.15IU/ml.  I haven't checked my Anti-HBs and so don't know whether I still retain the Anti-HBs at good level.

Grateful for your expert advice on what should I do next.  I am still on Entecavir 0.5mg daily.

Many thanks.

Regards,

C Y Or

[stef2011]

once we know how much it relapsed we can say if re-treatment is urgent or not

for example if you relapsed to 10iu/ml it is very probable you will gain back immune control slowly

also try high dose vit d first making vitd25oh 100ng/ml and pth 10-20pg/ml (if target pth is not reached increase vit d to more than 150ng/ml, during this supplementation avoid milk and dairies and increase water to 2.5l per day, keep an eye on urine calcium too although 99% it won t rise

as to curcumin i dont know if that is ok, it has antinflamatory effect so according to the balance of immune system it can boost or suppress immune response.green tea, 4caps of cpffee per day and juices ok for sure

[mustthinkpositive]

Yep, it's a tough break. IFN is no picnic really. Every week you have to man up and take the shot. You have experience in that now but are you willing to go through that again? I would imagine your HBsAg will be in the low level.

I would give it another shot. As it's been done by trials, IFN can be a 96 weeks treatment plan as well.

I also suggest many things to boost immune function such as Vit D3 daily (at least 3000iu daily), herbs like curcumin and garlic, regular green tea and lots of vege juice.

[cyrus131]

My ALT did go up to some 90+.

My pre-treatment hbvdna was undetectable and HbsAg was 456iu/ml.

My doctor is still skeptical about the effectiveness for another course of interferon in my case.  If I can't convince him, I will need to revert to more expensive private doctors.  Should I restart treatment and when?  I last finished 48-week interferon in mid March 2014.

[melcul]

hei cyrus, sorry to hear that you relaplsed, but it is good you checked it and find out soon, i dont think it will be a problem for you to clear it, as you took so many years entecavir. i wanted to ask you if you remember, can you tell me your hbvdna or hbsag quant before you start taking entecavir ?
thanks .

[mustthinkpositive]

Hi there,

Sorry to hear that. I hope my next appointment in 4 weeks time is OK. My surface antibodies climbed from 55 to over 300 in 10 weeks (week 38 to week 48). Fingers crossed it remained so.

Just wondering that since Paris2013 did not experience any elevated ALT during IFN treatment. What about yourself? Did your ALT level goes up?

My ALT was still on 125 2 weeks after IFN.

[andrey19]

you can try extended interferon course off lable or find doctor in Singapore for prescription (extended course is very normal there, I can recommend you a doctor).

[mike9111]

I know Cyrus that it is frustrating when you almost cleared but relapsed, however look at the positive side of it that you responded to treatment and you are more likely to clear than many of us who still have long journey

[cyrus131]

Dear studyforhope,

Thanks a lot for your prompt advice.  While repeating IFN for another course is off the guideline in Hong Kong, I am not sure if there are doctors who will prescribe me a course of zadaxin.  Btw, how long is a course of zadaxin?

My doctor just commented the effect of repeating IFN is very limited in my case as "No one know if my immune response can be further enhanced by
repeated another course of interferon."

I think I will check my qHBsAg before considering my further treatment regime.  

Many thanks for all your support!

Regards,

Cyrus

[studyforhope]

ifn or likely better a course of zadaxin. if you are in hongkong, it is available there.

[cyrus131]

Dear studyforhope,

Thanks for your expert advice.  So you mean it is better to repeat another course of interferon?

Regards,

Cyrus

[studyforhope]

let us wait intil your quant hbsag comes back. if your dr does not want to give you more interferon then there is very little that you can do to change the course. taking antivirals will slow the regrowth of the infected cell number.

i think if you retreat later with ifn you will have a response again. It is the lack of the proper epitope tcell clone combination and an insufficient cytokine milieu to keep the tcell clone in an effective state that limits the permanent internal control.

[andrey19]

My opinion is that your hbsag titer went below cut off level (<0.05) while paris2013 was 0.09 iu/ml almost below. Both yours and her immune system should establish permanent control of hbv but for some reasons that did not happen. Meanwhile you both continued taking entecavir after pegasys but it did not help to keep hbsag cleared.

See page 18 of below presentation: http://www.aphc.info/pdf/2014/Luncheons_13012014/S-251/Jorg_PETERSEN.pdf  

Some people clear hbsag with Baraclude mono without any relapse in the future, this is really possible while we have two members here that cleared hbs and relapsed. I already start thinking that hbsag relapse is irreversible.

[cyrus131]

Dear Andrey,

Thanks for drawing my attention to Paris2013 case.  The only difference between me and Paris2013 is that I achieved HBsAg undectable (I don't know whether it is equivalent to clearance) and then attained the Anti-HBs at 22mIU level (I know it is low but my doctor would not prescribe further interferon and I was too stupid to think I had already won the battle of HBV).  Now I was tested positive for both HBsAg and HBeAg.

I haven't checked the HBsAg quantity but will do so these few days.  What do you think about Paris2013's doctor about it is useless to repeat interferon as it appears that we (me and Paris2013) have no permanent control on the HBV.

Would studyforhope please kindly advise.  Many thanks.

This disease is indeed very frustrating!!!

Regards,

Cyrus

[andrey19]

did you check your hbsag in quantity again? By the way Paris2013 also relapsed after extremely low hbsag achieved by interferon and anti-hbsag development as well.

[stef2011]

another thing i dont have time to read the full post now but if you had only 48weeks of pegintf i strongly suggest to restart it.the most potent effect of peg on immune system is between first and second year (not shorter or longer), so this might be the best choice togheter with vit d or simvastatin as some of us are trying

[stef2011]

first of all check the level of hbsag and hbsab, after we have this result i would go for hbv vaccines, zadaxin or gcmaf if low.if high another round of pegintf

is your vitd25oh kept at optimum levels around 100ng/ml?of course this is mandatory for immune function and if low must be corrected as soon as possible

as to the use of entecavir or tenofovir i would wait for the expert opinion of studyforhope.i personally prefer tdf because more potent