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Entecavir + Interferon combo
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
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Dear all,

This morning, my wife helped me to do the interferon injection.  When the needle was in my belly, she pull the syringe to see if there is blood coming out.  She did and saw no blood.  Then she performed the injection but when she pull out the needle, we found that trace of blood was inside the syringe.  Just want to know if the interferon was injected into a blood vessel, any adverse effect or will it render this injection useless?

Thanks a lot

Regards,

Cyrus
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Bleeding from small vessel. not significant.  You have to cannulate a vein properly like a medical train person to get any sizable volume into a blood vessel.  
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To Cyrus,

How is your other blood work like ALT and WBC/neutrophils level? Your treatment seems to be on the right, positive track and I wish you all the best.

Correct me if I am wrong but did you miss one dose because of flu?

Thanks.
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Dear Stefano and Studyforhope

I just got my latest qHbsAg result which indicates my level is <0.05 IU/ml as at 19 February 2014, meaning negative.  My last qualitative test on HBsAg and HBeAg was still positive as at 6 February 2014.

My questions are whether the threshold in determining positive / negative is different for the quantitative and qualitative tests?  

What should I do now?  e.g. check for whether I have Anti-HBs or to inject Hep B vaccine in order to achieve s-seroconversion?  If I do not develop Anti-Hbs, should I continue peg-interferon injections beyond 48 weeks?

Many thanks for your kind advice.

Regards,

Cyrus
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congratulations Cyrus .Thanks for posting the data .
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Hi Stef

The Hbsag levels of Cyrus and Otan were same . However Otan cleared it in 16 weeks . Whereas the Otan DNA levels were quite high at the start . Could it be the Simvastatin effect worked for Otan .

Thanks
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so happy that you cleared hbsag too, which week is 19 feb?

don t worry about difference in quant and qual, it doesn t matter and is not relevant here.now you need to monitor hbsab level and keep peg until a good level of hbsab is achieved

if you dont see an hbsab in 2-3months you can also try the following to stimulate immune system:
hbv vaccine
zadaxin
gcmaf
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also consider to keep entecavir for 6-12 months even when hbsab becomes detactable, there are no guidelines for this but researchers that cure patients this way keep antiviral for 6-12 months after peg is finished just to be sure no relapse
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there are 2 members here clearing hbsag in combos where simvastatin is present:
otan peg+sim
another member i dont remember now: tdf+sim+gcmaf

too little patients to say it helps but since we know it prevents hcc, fatty liver and has few sides if any, it can be tried by others to confirm

both otan and other member had low hbsag, i think this is the main factor for peg response but this said sim may have a role or not, we need to find out
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About 45 weeks.  Should I check the HbsAb level? I am afraid my doctor will not allow me to inject interferon beyond 48 weeks.
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you absolutely need to keep peg beyond 48weeks until we have good hbsab, check this in advance and look for another doctor if there is any trouble

i remember otan got n touch with a researcher/doctor in HK or singapore, check her posts, he was very expensive but studying and treating to make hbsab once hbsag is neg
he is using peg, zadaxin and hbv vaccine

or simply look for another doctor willing to go over 48weeks

the maximum peginterferon strength is after 48weeks, in the second year of use, and this is quite normal to use 96weeks on responders

you may also start the hbv vaccine or zadaxin before 48weeks if these are non prescription in your country
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Dear Stefano,

Thanks.  Since I have hep B since birth and I am now 40 years old, is my chance of getting liver caner and fibrosis the same as before?  Should I continue to have ultrasound screening of my liver every 6 months as before?

Best Regards,

Cyrus
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is my chance of getting liver caner and fibrosis the same as before?

no in any case, also data we have is too little to say hcc risk is increased, we may say this on cirrhotic patients.i suggest you have regular nagalase screening if nagalase is normal there is no way to develop cancer, it also takes very long time for cancer to develop after nagalase become abnormal

Should I continue to have ultrasound screening of my liver every 6 months as before?
yes and if you add nagalase monitoring too you can be sure to have no surprise
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Dear Stefano,

Just had a follow-up yesterday and got my latest blood test result

Dated : 11 March 2014
HBsAg : Negative, HBsAb : 22 mIU/mL

I will continue to take Entecavir 0.5mg for further 6 months.  Is this HBsAb level low and do I need to further boost the immune response by injecting vaccine like Otan did?

Also, I have injected interferon for 49 weeks and I still have 1 spare dose in my refrigerator.   Should I inject it in the coming week?

Your expert advice is highly appreciated.  Many thanks.

Regards,

Cyrus
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very good! Congradulations!!! By the way do you have data on you liver stiffness before you started treatment and now?
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Dear Andrey,

Before treatment is 4.2Kpa (Fibroscan) and this is my last test.  I have done Fibroscan recently.

Regards,

Cyrus
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this is fantastic!!! I wish my hbv could end up in this way!!!
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have last injection, of course

hbsab 22miu/ml is too low, it would be best to keep etv for 6-12 months and if hbsab will not rise to 200-250miu/ml it is best to have hbv vaccine

is your vit d level good?
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Congrates cyrus.
I am also chronoc hepb patient
my latest blood report are here
plzz give me advice how to cure hbv
Hbsag confirmation test positive.
Antihbc total Reactive (CMIA) 12.86
antihbc IgM non reactive.(CMIA) 0.5
Antihbs Non Reactive.(CMIA) 0.81miu/ml
Hbeag Non Reactive(CMIA) 0.36
Hbv Dna Undetechable(PCR) <3.6 iu/ml

ill wait for ur valuable comments
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Steff, what are your supporting points for keeping etv after testing hbsag neg on inf treatment?
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that s guidelines once hbsag neg and hbsab pos the antiviral must be kept to normalize and consolidate immune response (remember cccdna is still there)

i believe only italian guidelines took care of this, very few countries around the world are actually curing hbv patients and taking care of consolidation...maybe only few words about this by researchers/most expert liver specialists
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I think there is always chance for hbsag relapse even when you test neg after inf course and in order to decide weather you need to go for next peg shot or maybe even go prolonged course you need to monitor your hbsag kinetics while on treatment. Just imagine if you were still hbsag positive on week 44 and started bebing neg on week 48. Is it wise to stop inf right away? or maybe prolong inf for a couple of month or so?
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How exactly can one find a good, non biased,  knowledgeable doctor?? Thanks
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good to see you folks are getting good responses :)
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I HOPE THE DOCTOR CAN FIND CURE OF IT. I AM HOPEFUL TOO
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Dear Stefano and studyforhope,

Sad news indeed.  I rechecked my HBsAg on 10 September 2014 and got my result today that my HBsAg is 'POSITIVE' again i.e. my Hep B relapsed!

I have discontinued my interferon as scheduled (after 48 weeks) after I developed Anti-HBs in March 2014.  I have not ceased and still continued to take entecavir 0.5mg daily as a precaution advised by you.

I did not get the vaccines (which I am terribly regretted).  Kindly let me have your expert opinions.  Many thanks.

Regards,

Cyrus
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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
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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
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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.
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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
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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.

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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.
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Dear studyforhope,

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

Regards,

Cyrus
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ifn or likely better a course of zadaxin. if you are in hongkong, it is available there.
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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
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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
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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).
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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.
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9624973 tn?1413019730
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 .
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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.
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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.
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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
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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
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9624973 tn?1413019730
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
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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
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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.
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Dear studyforhope,

Do you need I still have detectable Anti-HBs?


Cyrus
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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.
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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
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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.
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