The lesser of two evils

Hello all.

Time to pick my poison has arrived :/.
For over 6 months my ALT is hovering near 300 (after 27 years of immuno-tolerance with very high VL).
I have to face the enemy now.
State of liver is good (no fibrosis, a bit fatty, a bit of portal tension,  but OK otherwise).
VL is still very high (decreased in these 6 months of immuno-activity only 1 log from log9 to log8).
Doctor said i have 2 choices: pegasys 48 weeks (the only thing that can cure me for real) or tenofovir for ... ever ?
Because my VL is still very high I am not sure about the pegasys's efficacity at this stage. I know that taking pegasys could pay off in the long term (5-6-10 years) but the sides could be quite serious.
I know all the ups and downs of both treatment but I still have a dilemma.
I tend to favour the tenof. because of manageability (I am in the process of switching work places). I still have doubts though because I am only 34 and if I start with tenof. then its all open ended game.

One doctor said pegasys could cure me (not "will" but "could"). Another said that VL is so high still that ifn is of little benefit right now.

What I personally dont know is if the interferon is less effective after tenof. or its all the same ? Opinions ?

I was thinking to take tenof. for a while and then "exit" with 6 months of pegasys (when my VL goes UND).

Maximum health to everyone,

Death to cccDNA!

Million thanks,
F.

[4est]

on the other hand the pegasys is a safe way, you can interrupt the therapy at any point without any risk of virus mutation. (also for monitoring the pegasys efect you can spoke with you doctor about the Ag Hbs quantitative assay )

did your doctor consider also a combo (pegasys + Tenofovir) ?

good luck!

[focault]

True that pegasys has no sides (when it comes to hbv itself). But it does have a lot of sides otherwise (chronic fatigue, anxiety, depression + many more). Some of them are permanent. I have the hbv flare only for 6 months but I am still hbeag+ and my VL dropped (without meds) only 1 log until now. My understanding is that interferon is very very inefficient with high VLs. It could may be OK with 4-5 log but with 8 ? I have a feeling I risk the sides for nothing.

The doctor has not considered comboing. He is very conservative and probably only goes known routes. Is there any data available about comboing tenof. + pegasys ?

My doctor seems to aim pretty high (e.g. "curing" me) but is he realistic in expectations with the pegasys with this VL ?

Do you think 6 months is too soon to have hbeag- ? May be I should wait a bit for a pleasant surprise ? I know hbeag seroconv. are better if they are got naturally.  My liver is in very good state (no fibrosis, mild inflamation (inflammation)).

Thanks,
F.

[stef2011]

bit of portal ipertension

i wish this is a mistake or uncorrect report...portal hypertension is a complication of very advanced decompensated cirrhosis, hope this is not related to cirrhosis.do you have fibroscan readings (although at this stage with alt 300 inflammation may be the most of the reading and not fibrosis) or biopsy

my suggestion according to our experience with other forum members:
prepare for the war by making 4weeks
vitamin d25oh >50ng/ml taking d3 10000iu daily and then dose to keep that level
simvastatin to get cholesterol total <150, ldl50
alinia 2g daily or 2.7g, one pill every 4-5hrs with food

this pretreatment will make response to tenofovir and interferon much stronger, especially interferon.lower d3 when levels get higher than 80ng/ml to a dose to keep levels 50-60ng/ml

after these for weeks of alinia mono add tenofovir to the combo above, response should be extremely fast like 4-12 weeks to get undetactable

after you reach undetactable for 6months or more add interferon to the combo and just follow hbsag quantity

to make all this extremely useful it would be good to check hbsag quantity, hbeag quantity, hbcab quantity both igg and igm

the chances of hbsag svr should be the highest on this combo for an hbeag positive, just consider that a simple combo of interferon+lamivudine only made about 30-35% svr at 2 years of continuous combo....

i just had info from clinical trials that gilead lucked out on trial tenofovir+interferon, they didn t expect this from the study.....
about 25% hbsag svr at 1 year with interferon 24 weeks and then tenofovir....if you consider we add alinia, vit d and low chol hbv is having the maximum trouble to win.

if there is a lowering hbsag after 24 weeks never stop the combo until hbsag is negative, even 2-3 years of interferon unless sides are so bad, in that case you can stop interferon for short periods and then restart as a small trial did getting most of responder to svr

[stef2011]

you have to start now because hbv is already working on the e-minus mutants to escape your immune response (precore , bcp mutants) which may already be present

anyway the sooner you start the better the chances, hbeag seroconv is of no use and if due to the mutants even worst

check hbcab igm quantity, if higher than 0.2s/co thisis the moment with the highest chances of interferon hbsag eradication, timing is important because once hbv makes immune escape to your breaking the tollerance all treatments  have lower svr rates

if your doctor is conservative he is of no good use, check if you have a researcher close to your area and work with him on the project above

[stef2011]

we have experienc from a guy on interferon+alinia 1g a day and his response was a bomb when he added alinia to interferon, before alinia interferon was a failure and about to stop

too bad the doctor thought it was interferon to make the huge hbvdna drop in weeks from 8-9logs and hbeag drop to close sercovertion and put the guy on the highest interferon dose, this made severe depression sides and guy stopped all meds...so a good doctor is needed to monitor the combo above

this was our schedule with pisa researchers using entecavir instead of tenofovir...beng on cirrhosis interferon canbe dangerous so i prefered to wait for interferon lambda and try gcmaf frst

[focault]

No fibroscan here but I had biopsy (exactly at the beginning of the flare) and the Metavir results are as follows (may be I expressed myself wrong way about hypertension ... I think its rather "inflammation")

Representativness of the sample .... Good
Portal inflammation (0-3) ... 2
Interface inflammation (0-3) ... 1
Lobular inflammation (0-2) ... 0
Inflammation Activity (0-3) ... 1
Fibrosis (0-4) ... 0
Fat (big areas) ... 5%
Fat (small areas) .... 30 %

Am I correct about OK-ish shape of the liver?

Soo ... what do you guys think ? To interferon or not with this 8 log VL ?

Thanks

Focault

[stef2011]

tenofovir before interferon is needed because hbv is able to suppress interferon, making hbvdn very undetactable has shown to break this ability of hbv to make resistnce to interferon, on some making hbvdna und can also awake some immune response that interferon can lead against hbv

tenofovir mono has about 16% hbsag eradication at 3 years or more but monotherapies have shown to be a total failure until now, keeping hbvdn und is not our goal, that's just drug makers goal to keep us paying

[stef2011]

liver is perfect

direct to interferon may be a failure, better alinia+tenofovir first and then add interferon....nothing to lose and all to win from this strategy

you can even stop all drugs after interferon if there is no hbsag decrease or if it is too slow and remain drugs free until the next flare (interferon can gain immune control of hbv for some time in non responders)

[focault]

OK then:

Step 1: overture with strong D vitamin and 2g/day alinia (lets see how to get hold of it)
Step 2: tenof. mono for a while until UND (1 year ? 2 year ? 3 years ? (keep alinia and vit D on)
Step 3: Coup de grâce with 6 months of pegasys (after HBV DNA and HBsAg decreases for a while)
Step 4: dance on cccDNA's grave

Of course since this is a very old enemy (since I was a child) I will keep tabs on how it goes.

Am I correct to think that since I have 8 logs of HBVDNA will make interferon less efficient ?

Last question: I had 6 months of monitoring and in 1 week I will start treatment. Too late ? Its according to some EASL guidelines. Do mutants appear so fast under immune system pressure ?

Thanks guys,
F.

[4est]

regarding the Vitamin D level: http://www1.easl.eu/easl2011/program/Posters/Abstract581.htm

I know that we are discusing about Tenofovir and in poster is Telbivudine but I think that both drugs are NUC's and use the similar ways, so in my opinion vitamin D is a good thing. (I also have a clear indication on vitamin D for HBV from a very good doctor)

anyway, good lock on your therapy, and keep us posted with the results if is possible.

[stef2011]

Step 2: tenof. mono for a while until UND (1 year ? 2 year ? 3 years ? (keep alinia and vit D on)

this is the weak point....we dont know when and who responds to interferon but a poster from latest intl congress in berlin found  interferon non responder to become responder after hbvdna und on entecavir and eradicate hbsag
another one on interferon+entecavir+tenofovir cleared hbsag too

maybe the degree of intrehepatic hbvdna suppression might tell.if i was you i'd keep it 6-12 months after become und

Step 3: Coup de grâce with 6 months of pegasys
yes and stop if hbsag doesn t decrease by 6 months, keep it until hbsag negative if hbsag decreases

[4est]

a study that was presented in posters session on EASL 2011: ADD-ON OF PEG-INTERFERON TO A STABLE NUCLEOS(T)IDE REGIMEN LEADS TO LOSS OF HBS-AG IN PATIENTS WITH CHRONIC HEPATITIS B

http://www1.easl.eu/easl2011/program/Posters/Abstract603.htm