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233616 tn?1312787196

Il28b testing update

the profile has just changed and it's good for us, but requires understanding as it just got more complex.

I will try to explain and then give you the study.

We have long chains of encoding within our DNA. Each strand within that long chain has a combo of the basic proteins. When we speak of the alleles within a group, it is these pieces of data we referrence.

the patient only need know that how these proteins are encoded within your cells determines how strongly your body may be able to fight this virus.

Past threads have discusses the first test that became available as a genetic predictor.

Now labcorp (through Arup) is making available 2 single nucleotide polymorphisms rather than 1.
what that means is that we will know the Interleukin program within 2 of our gene programs, and have a better predictor of outcome.

Now here's where it gets tricky.

the original test some members already got showed a 2-3 fold increase in SVr with the right genes.
this test is known as the IL28b rs12979860
with this test the best combo to have is C/C, followed by C/T, and by TT being the worst.

Now they have moved up the chain to test one more set of alleles, and this test is call the IL28b rs8099917.
with this group T/T is the most favorable outcome, followed by G/T followed by GG being the worst.

now you see where confusion could come in. TT is least favorable with the test for one grouping, and most favorable with the group next door!!

here's the study:

http://www.natap.org/2010/HCV/050310_09.htm

now I just happened to have had this testing done and my results arrived today.

to my surprise I was CC  on the rs 12979860 and TT on the rs 8099917
it doesn't get any better than that.

this means that I should be able to clear with a PI added especially if I keep my IR down and get my Dietary restrictions in place.
It also means my diet had a great deal to do with why I didn't clear because I was extremely compliant on tx and my genes helped, so I should have cleared, except for being stage 3/4 which also may have lowered my chances.
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233616 tn?1312787196
as I've always understood it the biological half life is not just an indicator of time to reach steady state, but it the best indicator of clearance rates as well...

there are substances that clear in 100 minutes, 100 hours, 100 days and 100 years..

the operative biological half life does more than indicate when steady state is reached, it is how the Rx's are prescribed, it is why you have to take some things once a day, vs. four times a day, or once a month, etc.

a good example would be lorazepam vs. valium, one has a half life twice as long, meaning it only needs to be takes half as often as it not only reaches steady state (goes in) more slowly, but also comes out more slowly.

http://en.wikipedia.org/wiki/Biological_half-life

it get's more complicated than that, when the goal is to build up the plasma, but we were speaking of INF which doesn't stick around long at all, and needs constant replenishment as it used up quickly fighting the virus and also because our insulin cancels it out.
Ergo in my mind a pump as someone mentioned would be the best approach to avoid vasilations, and some would say peg, but peg had a end of week drop off that can be pretty severe.
It's not like I can guarantee it will make a huge difference, it's just that when you see short half lives, of 2-4 hours, you see more rollercoaster type graphs on the blood plasma levels and with INF this concerns me.
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Avatar universal
half life means the time it takes to get to half the original plasma level. I know it's not an exact correlary but if we start giving the math formulae we will lose everyone.

>>>>>>>>>>>>>>>>>>>>>

I don't believe I gave any math formulas. But, it is critical to understand that 1/2 life of ribavirin does NOT mean the ribavirin is gone in the time frame you stated. For a woman contemplating pregnnancy, they mutunderstand half life in order to time a pregnancy. I don'rt think explaining half-life a bit further would lose anyone here. ..... Actually I thought many were lost already.
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233616 tn?1312787196
forgot your one remark: sorry I rarely proof or even glance back

>>>>>>>>If you do it 3x a day you are only relying on some concept that it "kills" the virus. It does NOT. WE DO.  

What do you mean when you say WE DO, this is symantical.We have all kinds of white cells,Neutrophils, Lymphocytes, Monocytes, Eosinophils, and Basophils...our macrophages are the ones that sniff out the hcv viron.
Our interferon kills the virus by virtue of being a catalyst.
Our macrophages kill the virus once the INF activates them.
we have all kinds of white cells doing different jobs, what the inf does is act as the activator, it's a protein and our body can only make so much...so yes, we do fight it, but its the amount of inf getting to the cells that determines their ability to respond.

Obviously left to our own devices the body tries to mount a defense, this is why the spleen becomes enlarged, the whole immune system is in hyperdrive trying to contend with too little ammunition to fight the enemy. Enter injectable INF and now you have the bullets to go INF the macrophages to fight and WIN the war...well, not very well unless the tanks (riba) and the airforce (PI's) also step in.
But were you to return to no or little ammo, then unless you seriously maimed for life all those enemy soldiers and left them armless and legless, as HR's analogy once suggested, then you would be right back to losing battles in short order.
Does this answer help you??
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1491755 tn?1333201362
What ever you decide to do I hope it works for you.  That's the important thing.  Best of luck to you!
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233616 tn?1312787196
>>>>>>>>So basically it's saying SVR isn't really durable and we need that constant influx of IFN in our bodies OR we lose SVR?  

I don't get how you would have gotten that from anything said, but am willing to explore with you.
We need a constant high level of INF and RIBA to beat this virus into oblivion, and one could argue that whatever might be left, if any, would be an occult virus and not have the original virulency of the original strain.

folks that have achieved SVR I think have one of 2 things going on, either they literally had no surviving virons, or, as in MikeSimon's case they have a crippled occult form that cannot mount anything resembling what the wild strain was capable of.

I know occult virus was discussed a couple of years ago, and no one really liked those ideas, but Ibelieve HR and the other researchers were on to something.
We are only going to have our normal amount of Interferon once treatment is over NYGirl.
Our bodies are not equipped to handle viruses that make millions of copies everyday.
That's what all the discussion about the window of mutation was about, that closing the window, before any adaptation could occur was the best way to ensure no wild strain and no mutant AND no occult virus.



>>>>>>>The point of interferon is not to take it over and over to whack the virus and kill it BUT to train our own immune systems to do it right?
No, I would argue your interferon does not need training as I just said, it simply was insufficiant to the task, some people clear on their own because they get ahead of the virus due to optimal immune response, some do not and need INF to be added, but even there INF alone rarely worked, so entered the antivirals, and now protease inhibitors all designed to interuppt transcription phase, and eliminate the viruses means of reproduction, but once these are gone, we are not "trained".

>>>>>>>>> So we do HAVE interferon it's just a matter of training it.
Our interferon will always be scavenging for virus, it was before tx, it will after tx.
the trouble with this virus is it coats itself with lipids effectively becoming indistinguishable to the macrophages etc that are seeking out foreign bodies. By appearing as a "friendly" they evade detection and become the Al Qaeda within. Wolves in sheeps clothing.
If you do it 3x a day you are only relying on some concept that it "kills" the virus. It does NOT. WE DO.  

>>>>>>What happens when a dope addict stops taking heroin, oxy. dilaudid? Their body goes into WITHDRAWL and tries to fight that. It does not work out p3acefully.
What happens is eventually your body will produce enough enchephalins and endorphins again, on it's own. Same with INF.  Right after a round of tx you will have a deficit. If you recall HR addresses that critical period with the idea of tapering of the INF in order to allow the spleen to come back on line...which I did do.

>>>>>>So if I get a flu or cancer and my body needs the *IFN to treat that I will after 4 years lose my 'systemic virologic response' and thus need more IFN to keep dosing myself to keep everything at bay?
No, I think not. I think only a very few who reach SVR ever have that happen. It's only 1-2% that have that happen, and thats a statistical dead heat, meaning it could just as easily be a reinfection at that low number.
It's far more likely that if virus is detected again it will do so soon, and be virulent, unless it has been so injured that only very small numbers of very flawed mutations survived, and then they are like the weakest weed in the garden ever after. (as in MikeSimon's 40 L which hasn't budged in years). That's a occult virus, a weakened form unable to ever mount an attack again because it keeps producing dwafts or other legless spineless copies. That's the only way it makes sense to me, knowing how the original wild strain can return to millions of copies in just a few eeks, it's the only reasonable explaination...until someone does some DNA testing on the virons Mike and others like him have, and prove that they are carrying the original strain at those low levels, I will stick to the occult theory because its the only one that hold water in my view.

>>>>>>>>>I dont think so.  Supposition is not fact. Please stop trying to pretend this is scientific. it flies in the face of EVERYTYHing we know to be true.

When the subject of occult virus came up some very informed people gave this forum numerous studies, which were ignored not because they lacked scientific method, but because it was too horrible a thought for most of us, myself included. However in reading through this painful literature it eventually became a much more reasonable way to look at the disease. If you SVR for 6 months or more, you are not forever fighting the thing, you are basically cured, and if you have some lingering virons that can't ever get a foothold and mushroom, then they are maimed copies that will produced maimed weak offspring.
Once I got past the fear of that concept it became strangely comforting.

>>>>>>>Otherwise - we are all dead. Take your pick.
Well eventually we all are anyway, right? Sooner or later. But look, I think you beat the virus, I don't think you have any left, wild, mutant/adaptive, or occult. The only way you are going to get the thing back is if you got reinfected and overwhelmed at the same time, because you do have antibodies, which is the good point you made....it's in a sense the training you mentioned.
So, the bottom line is, don't get in an accident in a 3rd world country and need a blood transfusion. You could only be overwhelmed if you got a large exposure  by my reasoning at this point.
Of course I could be wrong, but based on how the viruses work, this is a fair assumtion. Of course, we do know of some virons, like polio, chickenpox, etc that stay in the system for life and reemerge when the immune system gets weak.
So the bottom line is no one can say for certain, the best any of us can do is hazard an educated guess. I have been unable to find any study showing SVR patients on autopsy with their original wild strain, so again I think you need not worry, I think you may have misread what I was suggesting.

mb
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Avatar universal
Why you just try it yourself and see how that works for you?  Then you can report back, low purines and all.  
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233616 tn?1312787196
I appreciate your observation but you are looking at one aspect only in my opinion.

The first method was to determine if higher doses made a difference as an induction and they didn't. You may recall there was more than one study about that idea, and they all proved punching hard early on does not work.

Reading on to the other methods and tests, and look James I know what the study says...in fact I read Infergen studys until my brain glazed over and developed a hard lipid shell...I choose this one to show both the frailty but the possibility.

the sides listed are the same sides we see with peg when weight based INF is not given.
All you would have to do is go back and read the sides that thin people who were being overdosed in here all had to know the truth of that, but look at it from the other side, we all drank the koolaide, we all took the peg knowing those sides were possible.

the point made later in the study was that lower doses might do a similar job. That even though this study failed at highest doses, and even though dosage and SVR are related, that 20-37% have SVR'd in former studys (not at such high doses) and that what this really shows is that they may be missing the forest for the trees.

My reasoning was, lets say we went to a different model that hasn't been tried, Say one where we break up the INF into a dose given 3 times a day, not the highest or the lowest either, but given 3 times, knowing the way the drug clears, and knowing that it's just like a lot of things that need dosing more often to work well. If something makes you sick at 24 mg, it doesn't mean you couldn't tolerate it at 18, or 16...or a lower number more often.

I'm on a drug like that now, and all the docs say I should be on between 30 and 60 mg per day with my condition, but I manage to get by on 15 mg because I space out small doses more often and in so doing I eliminate all the side effects for the most part and am doing better on 15 mg than I was on the higher doses they told me I must take.

my point here is, spread out correctly some medications can become as effective, and more problem free, at lower doses provided the dose is adjusted for it's half life correctly.
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179856 tn?1333547362
Mer

So basically it's saying SVR isn't really durable and we need that constant influx of IFN in our bodies OR we lose SVR?  The point of interferon is not to take it over and over to whack the virus and kill it BUT to train our own immune systems to do it right? So we do HAVE interferon it's just a matter of training it. If you do it 3x a day you are only relying on some concept that it "kills" the virus. It does NOT. WE DO.  

What happens when a dope addict stops taking heroin, oxy. dilaudid? Their body goes into WITHDRAWL and tries to fight that. It does not work out p3acefully.

So if I get a flu or cancer and my body needs the *IFN to treat that I will after 4 years lose my 'systemic virologic response' and thus need more IFN to keep dosing myself to keep everything at bay?

I dont think so.  Supposition is not fact. Please stop trying to pretend this is scientific. it flies in the face of EVERYTYHing we know to be true.

Otherwise - we are all dead. Take your pick.
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233616 tn?1312787196
half life means the time it takes to get to half the original plasma level. I know it's not an exact correlary but if we start giving the math formulae we will lose everyone.

bottom line is INF clears very quickly, half life is considered a standard for indicators of clearance,not just plasma levels, and ergo it's why docs choose one drug over another.
Particularly SSRI's benzo's, things where a short half life creats a yo-yo effect and all kinds of commensurate symptoms of low levels.

INF build very quickly when we have a virus, and clears quick as well..that's why sometimes you feel like you are getting sick...as INF goes up...then you are fine the next day...INF fell off when the body destroyed all the virus.

We invented peg not just because it provided a fix for the short half life, it also eliminated the patients who hate shots postponing their shots and sabotaging their tx.
It doesn't mean however that consensus INF didn't work better...CIFN...gee, why did they name it consensus...could that be a clue??  
The truth is that you will achieve a more level amount with 3 shots a day than 2 if you choose to go the CINF route, and, it might be that the stats of 20-37% for relaspe groups could go higher were they to do that.
After all this virus makes millions of new copies everyday, it therefore means the drugs used need to be and remain at steady state. With the riba this is a problem in the beginning due to slow absorption rate, but once it reaches steady state it's anything but.
With INF there's no perfect world regardless of type. The 7th day fall off is real, or with daily injections same thing. The question becomes how to best overcome those issues.
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1491755 tn?1333201362
Merry,

That's not what the study says.  How do you arrive at the conclusion.  Everyone in the study had a VL at 24 weeks, only one person #11 went UND at week 20 but then by week 24 had a VL again.  The study was a total failure.  All you have to do is look a figure 1.  

Take care and good luck.
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Avatar universal
You keep saying the inf lasts 8 hours and that is just not true with a half life of 4 hours.
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233616 tn?1312787196
FIGUY-exactly, and that why when I said on the thread trying to disprove Lindahl's discovery about amantadine that treating for half the normal time, and with every other day shots was ludicrous.  I don't really care that it was a small study, the idea that you could have gotten every patient to SVR  in any group, even if very small (which is how many phase 1 studies are...20 patients is not uncommon), to get to 100% was highly unusual, and it warranted a serious follow up study, which no one ever did. They just tailored the follow up to fail.
But then, I'm remembering that when billions are at stake the tobacco companys had no problem finding dozens of doctors to say tobacco was safe.

JAMES, read the whole study, sometimes if we don't read through a whole document we can miss the point....the end stats were great AND that was for non-responders...people thought impossible to cure,
and not only that, but the stats when they dialed it back were good too
meaning you don't have to stay at the high dose, just punch it hard to start with.
This goes along with a LOT of what is now thought and discussed about that initial window of critical time and the need to overwhelm the virus so it can't adapt.
Honestly, where have you ever seen 50% of non-responder clear...other than with this approach.
My point is that I think they would have even better results with an 8 vs a 12 hour regime, because the INF only lasts 8 hours, so why even give the viron any time without INF in the system. Take the same daily dose, divide it in 3, and then you aren't leaving the patient with 8 hours in every 24 with almost no INF.
If they were to try that they might get better results even at lower dose.
You can't rule something ineffective that cures half a populace formerly non-responsive.
You can say we need to tweak it to not get sides as bad, but to dismiss it is foolhardy.
Look at all the other chemos, folks hug toilets for weeks, lose their hair and much much more, and no one says well its ineffective!! Not when the end result is folks are living WITHOUT the cancer!!   So why conclude that with hcv? It does not compute.
mb
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96938 tn?1189799858
Yeah right, daily interferon 3 times a day.  Lady Gaga wouldn't even do that if she had HCV.
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1491755 tn?1333201362
Thanks for the study.  Tolerability was perhaps another reason for pegylation.  

From the study-

Despite use of blood cell growth factors and maximal support of experienced investigators, this high-dose of daily CIFN therapy in combination with a weight-based ribavirin dose was not tolerated due to serious adverse events. Most of the subjects required epoetin alfa injections for therapy-associated anemia. Even in the subjects who could tolerate high-dose CIFN therapy with weight-based ribavirin, sustained loss of HCV was not achieved by 24 weeks.

We cannot recommend this higher daily  dose of CIFN in combination with weight-based ribavirin. Our study effectively defines the upper limit of tolerability of daily CIFN dosage when used in combination with ribavirin. Furthermore, this high dosage of CIFN and weight-based ribavirin combination treatment was ineffective in eradicating hepatitis C virus in patients who failed previous pegylated interferon and ribavirin therapy.

The study concluded it was ineffective.
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Avatar universal
Ummm, if the half-life is 4 hours, you still have a quarter of the dose at 8 hours. It's not all gone. Shooting 3Xday sounds a bit dangerous to me. Your neutrophils should be undetected by day 4.
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233616 tn?1312787196
gee james, I hardly know where to start. FYI peg would never have been invented if not for compliance issues...and lets recall the whole idiot scuttle butzs that used to say 80% of meds 80% of the time was fine...both were they drinking coolaid...

look every year at ASSLD they stand around and compare rates...and poor countries that only can afford to treat once, or where patients must present thousands to be seen.,.still use CINF because if they can convince the patient to be compliant results are better...

and it's the same reason they offer some version here, Infergen, whatever, some CIFN...to retreaters...it works better.

here's one study where even non-responders cleared at a 50% rate when dose was increased...of course clearance is definitely related to dose, but sides get much worse so there has to be some give and take on docs part.
Personally I'm thinking of hitting it harder the first 2 weeks, and then dialing back a little.

http://www.hindawi.com/journals/heprt/2010/537827.html

there are lots of studies showing daily works best...note the drop off when they tried every other day....bad stats...that's why peg can fail...every body absorbs slightly differently.
if you have a high rate of absorbption, your end of week levels could be too low....it's not a perfect drug peg...it just eliminated the other problem, non-compliance.
I guess alot of folks hate shots, and some just get busy or space out for other reasons...
but the daily shots are still highly thought of in many circles.
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1491755 tn?1333201362
It sounds like you are making the claim that success rates are higher with INF as opposed to Pegylated-INF ?  Please provide a link to the study.  
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Avatar universal
My logic is focused on the PI because it's the power house.  It must be excruciating when some one's thoughts are bouncing off the wall to the point of erratic and no one gets it.

But I suppose the forum is for exchanging ideas even if those ideas are illogical and impractical to us mere mortal.

I like to think outside the box but not outside the universe. Then possibilities become infinite and there is no means to an end.
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233616 tn?1312787196
yes, I looked at that mini pump a few months back, and yeah, I know it's marginally better...I mean, it is the best really if you can bear an apparatus.

nygirl, it's really not hard at all. Look, the verdicts were in long ago that daily interferon had better result WHEN folks were compliant.
only WHEN, when is the key word.

some folks are afraid of shots, some aren't. I've had to do dailt injections for years now, so it takes me like maybe 60 seconds to whip out a syringe and pop my belly...one advantage to pinching more than an inch, belly fat has very few nerves, grin.

my reasoning is very sound here, the interferon only stays in the system for 8 hours, even still in countries where daily INF is still used the rates of compliant patients is higher than for peg. peg is only higher where you see non-compliance.

now my issue was why are they allowing for the 4 hour window with NO interferon?
if they are getting higher better stats with the daily injections over the weekly, it's because the peg end of week fall off is too great. Onviously the steadier the state the better.

ergo if you eliminate the 4 hour empty window, and go to every 8 hours, you'd at least be eliminating those times of NO interferon. you still are getting a higher level the first of the 4 hours and less high the second 4, but you would increase to almost steady state.

I like your guy's idea though of the mini, and think maybe the external pump for the first couple months might be doable....it would give optimum coverage, then maybe I'd switch to shots after getting UND when it wouldn't be quite so crucial.
I thought this would lower chance of infection because if the blood tanks like last time that could be a big issue (I got several infections last time, remember?).
But the blood won't take completely for a while, so it sounds good.

Not sure I'd want to do the whole year....I had to wear a heart monitor a while back...and it drove me batty in those 2 days...a whole year of that..yikes.

I suppose I should just ask for the pump though and then switch, if I tell them I just want it for the first couple months it would never get approved.
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Avatar universal
using an insulin pump to maintain interferon levels is a wonderful idea.  a diabetic nurse educator will be able to show you how to insert the cannula and maintain the pump.

btw here is the current announcement for the medtronic mini med pump trial for HCV
http://clinicaltrials.gov/ct2/show/NCT00919633

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148588 tn?1465778809
I can read the time stamp on your posts and know your sleep patterns are not those of mere mortals ;-) You're in good company along with Thomas Edison and other creative thinkers.

As to insulin pumps:
First, note they were using an *external* pump w/subQ injection.
Second, like the three-part-non-invasive blood test for occult HCV, it's too cutting edge to be commercially available yet, anyway. You'd have a hard time finding anyone to do the procedure.
Just trying to emphasize the point I've been trying to make for years - if half the money spent on developing PIs had been used to understand IFN better and develop better delivery systems, we'd probably have had the IL28B years ago and there would still be at least one PI for the FDA to scratch their heads over in the coming months.
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179856 tn?1333547362
Oh Merry my dear dear friend you know that i love you, you know that but what do you mean you are going to inject 3x a day?  Please, please none of this makes sense............get the PI, do the treatment please my friend stop second guessing this disease you know you cannot do that.

Diet, no drinking, healthy liviing yes but this time go with real science and stop trying to figure it out. The scientists do that! You want to get rid of this once and for all. I want to see you WIN this battle but guessing at things and doing this isn't going to get you there. Oh please.............please........I am seriously getting afraid for you. We've been friends for so many years, let the science dudes prove the science but just get tela or boce when they come out and WIN!!!!!!!!!!!!!!!!!!!!!!!
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Avatar universal
The Arup test for the TWO  Interleukin 28 B (IL28B)-Associated SNP Variants:is 2004680.

BTB
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Avatar universal
Just posting a link. As more silly research is done it most likely will remain a negative predictor, but who knows. At least it is one that people have any control over. While searching for any other recent discussion on this topic, I was happy to find this comment at the HCV Advocate regarding this study:

Editorial Comment: Although this report contradicts previous information about BMI and response to treatment, this study is limited in its power to be compelling. First, this is a small study, so more data are needed. Second, the research is retrospective, rather than prospective. Data collection from randomized, double-blind, placebo controlled studies carry more weight than data collected when researchers look backward at the data.

We know the drill: Don't overeat, don't drink and don't smoke.
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