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My feedback on Entecavir +Interferon combo

I live in France. End of 2004 (I was 37) I discovered that I had chronic hepatitis B when my doctor saw a suspect ALT flare and asked for an additional blood test.
These are the results I had in January 2005:
Transaminases: AST: 95 UI/l, ALT: 216 UI/l
HBsAg +, HBcAb +, HBsAb -, HBeAg +, HBeAb -
ADN VHB: > 35000000 IU/mL
Liver biopsy result: A1F1

In February 2005 I started taking Hepsera.
Transaminases lowered to normal values in July 2005. HBV DNA values also lowered.
Phosphorus went down due to Hepsera.

In December 2005 the HBV DNA started to raise again showing that Hepsera was no more useful. My doctor added Lamivudine (Zeffix) on top of Hepsera.

In June 2008 the HBV DNA became undetectable. My doctor decided to move to Entecavir (Baraclude) 1mg.

In September 2009 I had HBe seroconversion: HBeAb +, HBeAg -

In September 2011 HBsAg was 4087 UI/mL. HBV DNA was always undetectable.

In September 2012 my doctor convinced me to add interferon (Pegasys) on top of Entecavir (even if I was really afraid by the possible side effects). After three months (Week 12) of entecavir + interferon combo the HBsAg was around 700 UI/mL (I don't have here the precise figure). After six monts (Week 24) HBsAg was 39 UI/mL.

My next blood test will be end of May.
I have some side effects due to interferon and sometimes I feel very tired. Neutrophils are very low (once they went down to 600/mm3). But the results I had until now convinced me to continue my weekly injections (even if I don't like at all to do injections all alone).






114 Responses
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Avatar universal
You should still take regular Vit D3 as a general health, just 1,000iu a day (which is standard) can push up your levels.

Yeah, I was on ETV for nearly 2 years. I take them 1 to 2 hrs before breakfast. Someone here said taking them after dinner, when you are going to bed. So all these time you have been taking ETV with food? Not sure why you have to do that but the Dr and Nurses should point that out clearly when prescribing and also the Pharmacist should also point that out.

Yes, you can check your D3 levels with a family Dr. Most likely it has decline because I realised now that this vitamin is so deficient in many people that don't take supplements. When I was on ETV, my levels was 20ng/ml and I don't take any supplements. In 3 months before IFN (after reading it here from Stef - thank you Stef), I pushed it up to 51ng/ml by taking 5,000 to 10,000 iu daily.





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Avatar universal
Here is good presentation on hbsag kinetics after stopping nucs or intf (see page 18). Doctor is from Germany. Hope this helps.

http://www.aphc.info/pdf/2014/Luncheons_13012014/S-251/Jorg_PETERSEN.pdf
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Avatar universal
again as an italian worldwide known good hbv research said:
most liver specialists are stupid and just follow guidelines with no knowledge of the disease

many french doctors are killers because many patients died on hcv trials.i admire the courage of this man for saying the truth at a conference

so trust liver specialists only when you see they said correct things about latest research and when they are not arrogant, they are there to cure you and not for themselves pleasure.switch to another one if they dont fit this
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Avatar universal
it is dangerous to take etv with meals because absorption is low and this might induce resistance overtime,anyway you should be safe on this

the best possible thing would be:
start 10.000iu of vit d daily, this is a normal dose and half what healthy people can do in an hour of sun exposure.no tests required with this dose but i d choose a good lab and have the test.

vitd can be bought on uk online stores,bigvits uk is very cheap and fast delivery

entecavir 1mg or tenofovir or keep entecavir and start peginterferon as soon as possible
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Avatar universal
i d change doctor too many obvious very wrong things said

just have vitamin d test in the lab, what's the doctor to do with having the test?

entecavir cannot be taken with meals, didn t doctor advise on this?extremely negligent doctor again
Helpful - 0
Avatar universal
No, I'm not taking any supplements. Two years ago Vit D was 29.4 ng/ml. According to your post this is too low. But my doctor once said that Vit D has no influence on VHB (and it's difficult to insist with him and he stopped the discussion). I'll try to discuss about it with my family doctor, to have a Vit D blood test.
Up to now I've taken entecavir during my breakfast. Reading old posts I saw that I should take it two hours before / after the meals. So I'll delay my breakfast to see if I'll be able to stop the HBsAg increase.
Helpful - 0
Avatar universal
Are you taking any supplements like Vit D3? What's your D level in your blood?

I really think your immune system must be tip top, pre, during and after IFN. D3 levels must be at least 50ng/ml pre-IFN treatment.

Even with the boost of IFN (which is integral), your own diet and vitamins intake (selenium, D3 and zinc) must be consistent.

However, having said that, you are a responder to IFN. Just need another oomps! to get that HBsAb up high. Vit D3 supplements might just be the ticket. I was lucky to have my HBsAb going up every month from 55 (when it first appeared) to over 200 and now over 300.




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Avatar universal
never mined hbsag will be over.
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Avatar universal
What a complicated head screwing disease we have. I just pray one day we can have a cure and not need to wrap our heads around what is trying to eat us from the inside outwards.
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Avatar universal
Your situation is unfortunately not untypical.
Restarting ifn now might bring you a more permanent control of HBV remnants in the end, possibly depending on the length of ifn therapy.
While the immunological reasons behind these different outcomes are basically known, it is currently impossible to analyze this in an individual patient.  Availability of effective TCell epitopes combined with presence and proper activation of TCell clones is the true reason behind success or eventual failure of ifn mediated immune activation, a complex battle with numerous critical parameters.

In my opinion, the svr rates will increase once frequent vaccinations with an HBV core containing vaccine will be added in the phase of low virion presence (UND DNA LEVELS). This will add the missing stimulus to increase TCell recruitment in the periphery.
At this time such a core vaccine is in development in cooperation between Cuba and a french company, but availability is possibly far out.

Using available hbsag vaccines in the phase of low hbsag to boost hbsAB levels is likely only marginally effective. It must be understood, that even a high AB level is never completely protective against localized reinfection in close proximity of an infected liver cell. The core vaccine will hopefully trigger Tcells that attack the slowly growing clusters of reinfected cells in that situation, leading to a permanent control of the remnants.
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Avatar universal
if no relevant sides go for it again or change doctor, the response when hbsag is so low are very very high

i understand that if sides are severe it is not possible to keep it for more than 48weeks but in your case the only side can be expense if peg is not free

dont worry about the rise if it is less than 500-1000iu/ml the virus has very little strength
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Avatar universal
Hello Andrey, yes, I continued taking entecavir after stopping interferon.
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Avatar universal
Hello Stef, thanks for these explanations. At the hospital they also said that HBsAg must be kept lower than 1000 iu/ml. But it is increasing fast: at week#48 (when I stopped interferon) I had 0.09 iu/ml; then at week#60 it was around 6 iu/ml; at week#72 it was 30 iu/ml; finally the last results I had (week#84) was 300 iu/ml. Sorry, I don't have exact figures, results are just communicated orally to me.
Anyway I try to concentrate on the good news: peg-interferon seems to work well for me. So I'm ready to start it again if necessary, also considering that I didn't have heavy side effects.
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Avatar universal
Hello Stephen, yes, there is a typo. I wrote HbsAb instead of HbsAg.
HbsAg were at 3500 iu/ml when I started the combo trial.
Thanks for the link on the no-nuc clinical trial, I will check it. Your statement on the ALT flare corresponds exactly to what my doctor said.
About the results of the combo trial, the information I have is that people who had HBsAg clearance had also experienced a previous HBe seroconversion before starting the trial. I suppose that also having a low baseline HBsAg is an important factor, my doctor being surprised by the result I had (only until week 48, unfortunately...) starting from 3500 iu/ml.
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Avatar universal
as to the stopping all therapies now i think it is risky because you may clear or relapse badly both hbsag and hbvdna, in the second case all the years of nucs making hbsag lower and immune control are lost/wasted
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Avatar universal
the other good thing is that by restarting pegintf you will get hbsag undetectable for sure.i dont know if waiting or restarting as soon as possible can make a difference on results maybe studyforhope has an answer on this
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Avatar universal
i think the wrong in your case was stopping pegintf before complete hbsag clearance and stable hbsab, and this is a clear rule of hbsag guided therapy of hbv.of course being in a trial is very bad because you cannot adjust or add.the biggest mistake is also stopping pegintf at 48weeks and all studies showed that maxium effect of pegintf on immune system is between 48weeks and 96weeks (not less and not more).in mono peg 48weeks has about 7-10% of clearance while 96weeks goes up to 20-30%

anyway these are my suggestions and maybe studyforhope can add more:
keep etv now and monitor hbsag, you should not go to more than 1000iu/ml because there is immune control at these low levels

keep an eye on your vitamin d levels and keep them at 90-100ng/ml

restart peginterferon in 6-12 months according to your willing and sides had during peg

to avoid relapse it is mandatory to get hbsag und and hbsab to high stable levels like 250miu/ml, as suggested by studyforhope when hbsag is undetectable there are still millions of it in the circulation so high hbsab needed

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Avatar universal
bonjour
désolé pour c nvlls  vraiment c est etrange ,j ai croyez  qu une  fois les anti corps  apparaissent , c est bon ,puisque le system immunitaire a connue le virus et commence a lutté contre
vous etes en qu elle region de France?
mo aussi j ai l hepatite b et je crois que je vais bientôt entamé un traitement
bonne chance

  Hello
sorry for the bad news it is really strange, I have believed  that once the anti bodies appear,  the immune system is known the virus and begins fought against
you are in wich area of ​​France ?   I have the hepatitis b too and I think I'll soon start a  treatment
good luck
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Avatar universal
is it right that you continued taking entecavir after stopping interferon on w48?
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Avatar universal
I don't think you should be too disappointed. The effect of PegIFN has a very long tail, so the benefit may come later.
Can you please check your message:"Now I suppose that HbsAb will raise up to my previous value when I started the itf+etv combo, i.e. 3000 iu/ml. "
Is there a typo?
I think the "no nuc" referred to observations by doctors that after prolonged treatment with NUC and achieving undetectable hbvdna, some patients who stopped NUC had a ALT flare and then managed to clear HBsAg. There is an on-going clinical trial to test this:
http://clinicaltrials.gov/show/NCT01320943

So I don't think it is a therapy that will work for everyone.

Thank you for letting us know the results of your trial. We await details that may identify which candidates (those with low baseline HBsAg?) can achieve a cure using PEG + NUC.


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Avatar universal
I would like to help you with advice but frankly have no idea on what is best for you now.

Maybe studyforhope can join discussion and give some advice?

maybe starting interferon again would be best for her even doing it against her doctor?
Helpful - 0
Avatar universal
I would like to help you with advice but frankly have no idea on what is best for you now.

Maybe studyforhope can join discussion and give some advice?

maybe starting interferon would be best for her even doing it against her doctor?
Helpful - 0
Avatar universal
At week 48 when I stopped interferon HbsAb was 40 miu/ml.
I did not boost it with vaccine.
According to my doctor entecavir alone will not be able to hold HbsAg as it is now (300 iu/ml), he thinks that it will go as high as it was before starting interferon.
Helpful - 0
Avatar universal
Very sad and disappointing news! But could you share what was your anti-hbs titer when you stopped interferon treatment? Did you boost it with vaccine?According to your doctor will entecavir be able to hold your hbsag around 300 iu/ml as it is now without further increase?
Helpful - 0
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