My feedback on Entecavir +Interferon combo

[Paris2013]

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).

[grmr]

seems to be good.. are you infected since birth? what's your genotype?

[Paris2013]

In 2004 (when I discovered my illness) the doctor told me that, in his opinion,  the infection had happened 5 years before.
I don't know my genotype. I've checked on the web and I saw that this information is important because (according to Wikipedia) different genotypes may respond to treatment in different way. I should ask my doctor. But I remember that a few years ago he told me that my virus was common in the mediterranean area, so maybe (always according to Wikipedia) it is type D. But I should check with him.

[Magda123]

How about sides? Did you experience depression?

[Paris2013]

I did not experience depression. I don't know if it is because of my normal nature (I tend to be always optimistic) or because I have good friends (who are not aware of my illness but I prefer this way) or because I live in an amazing town or just because I'm lucky.
But I had to go through some difficult moments, in particular at the beginning of my  treatment. I always walked a lot but at that time I was unable to walk more than 15 minutes. And also I have sometimes some moments when I have a strange feeling in my head (I feel confused and dizzy). And my skin is very dry (this is another known side of interferon).
But I'm mainly concerned by neutrophils now: they are low (around 0,8 last month) and each time that I have a little bit of fever I start to worry.

[grmr]

do not worry.. i had 2 ifn course 135mg shot and neutrophils were always 0.6 / 0.85 no more..

[stef2011]

it is so good to see that you confirmed the combo trials and i see you had high hbsag baseline at 4000iu/ml when you started.so it is not important the hbsag quantity at 1000iu/ml or less but the number of years under antiviral therapy

you are of course a 100% responder and sure to clear hbv, as to neutrophils i just checked hcv community where they use intf combo as the only available therapy and have much worst sides than hbv.in case of low netrophils or low plts there are drugs to use before lowering pegintf dose and the values are neutrophils constantly lower than 500 and plts less than 20-25

http://www.medhelp.org/posts/Hepatitis-C/Low-WBC--RBC--Platelet--should-I-continue-treatment/show/1934195

the drug to increase neutrophils when less than 500 is Neupogen

i hop to have a similar response as you when adding intf, this will be my forth year on antivirals and your results push me to try pegintf add on even if my hbsag is at around 3600-4000iu/ml

[Paris2013]

To grmr: during the last three months I had similar values as yours for neutrophils (0.6 / 0.8) but I'm on 180mg pegintf. According to my doctor there is no reason to worry, as long as neutrophils are > 0.5 I will not lower the pegintf dose.
Stef, thanks for your advice on Neupogen. A good point is that I often do blood tests because I'm in a trial so I'm sure that if something is going wrong my doctor will have the possibility to react fast. By the way that was the main reason why I accepted to go for pegintf: being in a trial I can take profit of a complete follow-up (blood tests, checking-up with doctors, etc) so that I feel really confident.
As you could see in my first post, I have been on antivirals for more than 8 years now. Is this the reason why I'm a good responder? Or is it because I've already had a HBe seroconversion?

[stef2011]

Is this the reason why I'm a good responder?

there is no answer yet, the data from trials which are public show:
50% hbsag clearance by 48weeks, people on antivirals from long time 5-7years low hbsag baseline less than 2000iu/ml

90% response with very low hbsag by 48-72weeks les than 300iu/ml with most patients with 10-30iu/ml.in this group there were one patient with very high hbsag at almost 7500-8000iu/ml

10% non response on a patient using lam+adv for about 5 years

my guess from this data (that confirms your results too), is:
potent antivirals like tenofovir and entecavir can make response despite only 3 years of hbvdna suppression and high hbsag.the patient with very high hbsag was on entecavir 3 years only

low potency antivirals need many years for response and might not respond

the hbsag level may have little importance, potent antivirals rescue immune response by lowering t-regs and other effects, so that pegintf add on works anyway

i want to try imiquimod again with a daily suppository schedule of 12,5mg which i tried only 2 times for 7 days because of the high cost.if i see an immediate hbsag drop as it happened before i ll try to jump in the intf trial too or will see with my doctors if the combo can be used out of the trials too

[stef2011]

so to clear the trial results (which was in france too):

of the 90% responders:
50% cleared in 48weeks
40% reached low hbsag which will probably clear by following combo over 72weeks.the hbsag here is so low that even off pegintf they ll slowly clear with time, even off both peg and antiviral

10% no response, this patient should switch to tenofovir and then retry pegintf add on in a year or two so we may see confirmed if non response was due to low potency antivirals.
this patient has also low hbsag less than 1500-1800iu/ml so the low hbsag may not be the key for the combo response but the potency of antivirals and enough time to rescue immune response on these potent drugs

[Paris2013]

Thanks Stef. Your explanations are very clear.
In my case, I'm supposed to go for a 48-weeks combo entecavir + pegintf (currently I'm in Week 35). My doctor said that I will stop entecavir only if I  have a full hbsag clearance. Even with small hbsag values he thinks that it will be necessary to continue taking entecavir. He also said that usually pegintf will still be working even after W48 (after the end of the injections).

[imdrew]

My doctor has a different opinion, he thinks TDF for 1,5 years and then stop. If relapse happens that recontinue medication. I asked about the possibility of resistance if I discontinue and he said it's very low (the chance of happening).

Can you tell this to your doctor and tell me what your doctor said to me? My doctor is in Malaysia btw.

[stef2011]

see the experience of otan and other in the forums and comments by studyforhope researcher, lowering hbsag to very low or undetectable does not mean clearance of infection because cccdna will stay in the liver cells anyway, we can only achieve full control of the infection by a high titer of hbsab which will block reinfection by the remaining cccdna which will be totally cleared by decades of full immunity

this is to say do not be tricked by less updated liver specialists, pegintf must be stopped when hbsab develops and not earlier.pegintf course is now known to be best at 96weeks since years but helathcare and insurances push to the 48weeks anyway........

so if you can by any means do not stop pegintf until hbsab develops, if the antibodies are not formed when hbsab is und t-cell response can be rescued by zadaxin and repeated hbv vaccines.
the best hbv vaccine is available in israel pharmacies but zadaxin+hbv vaccine sold in europe should be enough

once hbsab is high you must keep monitoring the levels in case it falls und again and hbsag develops back, 6-12months of entecavir even after hbsab is developped is a good choice, this is what research centers do

[stef2011]

tdf can t clear hbv, in 1.5years it wount have any effect

the minimum time to clear hbsag on tenofovir has just been reported by a study and is 17years, entecavir 35years.......your doctor is very stupid and you d better change it right away and apply the combo sequential therapy as the studies are indicating for hbv cure

[Paris2013]

I've already had this discussion with my doctor. He said that it is too risky to stop the entecavir before a complete clearance. A virus mutation is always possible. I also remember that when I started taking antivirals eight years ago (it was adefovir at that time) he told me that it was a lifelong treatment.

[StephenCastlecrag]

Stop TDF after a period of undetectable hbvdna then wait for a ALT flare to clear the virus is the subject of an on-going clinical trial. The trial was prompted by the observation that some patients who stopped TDF after a consolidation period of undetectable hbvdna sometimes experienced a flare, but then cleared the virus. I am not sure about about "1,5" year, most likely it should be "1 to 5" years. You can ask your doctor whether he/she is following this clinical trial.

[stef2011]

i dont think that dr even knows about this study, 1.5years is not enough at all to make any change to both immune system or hbv in the liver, to ave such response longer periods are needed and also fibrosis checked

[imdrew]

This the agony that we South East Asians have. Things are even worse in my country where most doctors are still recommending Lamivudine "to start things off and get the next medication ready for resistance development".

It's not even about the money anymore (how doctors are just selling drugs), it's just downright stupid and we're paying for it. And I'm having a hard time finding doctors who use the combo treatments. Even harder to find doctors who use add-on treatments.

Oh well keep on looking I guess.

[Taj82]

Dear what was your ALT level when you started ifn+ent combo?

waiting...for your response...........

[Paris2013]

During all these years with antivirals I had ALT level around 20 - 25. Never more than this. ALT did not change with interferon. My doctor was expecting a ALT flare demonstrating the effectiveness of interferon but I always stayed around 20 - 25.

[joc2011]

Did you have any issues with Blood pressures while on Entecavir? Been on Tenofovir for 3 years now and experiencing a rise in blood pressure. Managing or lowering this hasnt been easy. I hear its due to the fact that as the kidneys try to eliminate the TNF, over time the blood vessles in the kidneys begin to constrict, leading to increases in blood pressures.
I am considering making a switch to Entecavir. What do you all think?

[Paris2013]

No, my blood pressure is normal. I did not know that such a risk existed, this is an additional reason to continue the entecavir + pegintf combo hoping that I'll be able to stop both after the 48 weeks.

[stef2011]

do you have hbsag quant baseline before pegintf add on, sept 2012.

this is to be sure pegintf add on started with a high hbsag, the test from 2011 is not reliable and hbsag could have lowered from 4000 to around 1000-2000iu/ml

another consideration is you were hbvdna und 4years before pegintf add on since resistance to adefovir and lamivudine add on could not make hbvdna und before june 2008

your example is very good we may have 2 points as thought from the other trials:
tenofovir and entecavir need less time like 3-4 years of hbvdna und to resucue immune response before pegintf add on

hbsag does not need to be 1000iu/ml or less to have a pegintf response

[Paris2013]

My doctor asked for a blood test with hbsag quantification at the beginning of the trial (September 2012) but I don't have the results here at home, the doctor kept them. I remember he said that hbsag was around 3500 but I need to confirm, I'll ask him next time I'll see him.

[veteranB]

Guys those developing high blood pressure on nucs  drink more water first. And start drinking Habiscus tea and beat root juice with L - Arginine. I took my blood pressure down slowly to a more reasonable levels. 135/85 seems to be ok to me. But it is not 160/100 .

This is actually another proof why we dont needs these nucs. They are too toxic and high blood pressure is the result from toxicity. And the fact that nucs damage kidneys too.

But we need to constantly detox when on these drugs. Stay on a diet. Increase vitamin and mineral intake. Like Stef here said.

But on blood pressure habiscus tea works.

But I too would like more info on how to reverse blood pressure to normal  and understand the mechanism of how NUCs raise blood pressure.