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.

[Bali05]

Congratulations on the good genes !

Imagine you would have known this on your first tx.

It is very interesting how someone with a viral load of 300K @ wk16 can be CC type.
Interferon is the powerhouse that drives down the virus and even if you had a
Riba absorption problem on your first tx a 5.48 log drop from wk16 to wk24 by solely
increasing Riba concentration seems highly unlikely at that stage.
Were you IR on your first tx ?

You mentioned on your other post you had a breaktrough , 300k wk16 and than went UND by wk24.
What PCR did you use on that wk24 UND ?
In order to have had a breaktrough you must have been UND first. Are you saying your
VL started rising before you became UND ?

Would be interesting to see exact  stats from your first tx. Baseline,wk4,wk12,wk16,wk24
VL , HgB , Abs. Neuts and glucose.

[Trinity4]

"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."

Yes, fibrosis stage was a big factor in relapse, for you and for me. So was age and BMI in your case.  I hope everyone that reads your thread does not believe that if they follow the dietary restrictions YOU believe will thrust them forward to SVR it means they WILL achieve SVR.  You are not doctor and you can't prove your theory that high carb, low protein intake and whatever else you add or subtract to your dietary intake is the key to success.  Sharing information is fine, but people should know not take things that you write literally and apply it to their treatment and expect stellar results because much of what you write is speculation.  The only thing any future HCV patient can be certain of is that the PI they take is the heavy hitter.  Being a CC, changing diet and adding PI still does not mean SVR will happen and people shouldn't be mislead into believing so.

My advice to anyone is Buyer Beware!  Don't believe everything you read.  It's nice of merrybe to share her thoughts but it isn't necessary to alarm yourself if you don't follow her protocol.  Everyone is different and nothing ensures SVR, not even a PI.

Trinity

[desrt]

Non response to peginterferon alfa and ribavirin in IL28B CC & CT patients can be overcome by high dose continuous interferon alfa-2b administration in combination with ribavirin for chronic hepatitis C

http://hepcassoc.org/News/article243.html

(Lifted directly from Susie's site without permission. Sorry Susie, I was getting the PegAssist and Commitment to Care phone #s through your homepage because they're so darn accessible there. My compliments to DayLilly.))

[scaredycat7]

Hopefully, everyone takes what ANYONE says with a "grain of salt" -so to speak.  THere is just so much new information coming out all the time -well, some of us DO want to know it all. We know it could be disproved and day -coffee is now good! so is chocolate!  But everything in moderation and nothing suggested in the above or the riba absorption thread suggests anything radical.  If my treatment fails, I too will be searching for answers and trying to help others succeed. I personally plan to be sure to eat some riba absorption foods with my dose and avoid the others -but just at riba time.

As another IL28B CC person, I am glad merryBe brought me to earth.  I am treating with the Lambda,  very compliant,  have very little liver damage, exercise, but, have my age (over 50) against me.  Still, I thought for sure I'd clear.  We'll see.

I am so grateful for the people that have the patience to read through the medical jargon and point out to me that there may be something important here (merryBe). And for the people that say "watch out" (Trinity4).

Yours in the struggle-
sc7

[FlGuy]

"It also means my diet had a great deal to do with why I didn't clear ..."

Now, that's a giant leap for mankind.

[it'sallgood]

thanks for the update.   had the original test done, came back as CC and figured it meant i was a Cool Cat and tx would be a success.   nothing like a little dose or reality.
eroc

[nygirl7]

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

Jez Merry you should totally have cleared the first time. Do you think it's possible that somehow the HGH or something acted somehow negatively to prevent it?  With those test results you would think diet or not you would have cleared early and been done with this by now?

I guess it shows even armed with special tests, diets, info etc. it can still happen (relapse) but I would honestly think SOMETHING had to work against these great results!

(I bet i was a TT which is why it took so long for me, too bad I can't get this test now. I mean I hardly ate anything but ice cream so the purine concept wouldn't apply to me unless it is because it was cows MILK or something...I wonder if my doctor would order it he never knows what I am asking for really and might just throw it in - I could tell him it would be helpful to other patients in t he future and explan it to him......)

[Trinity4]

I always like to refer back to the limitatons Labcorp states about their tests:

"IL28B genotype is only one of many factors that can influence response rates to pegylated interferon/ribavirin therapy in HCV genotype 1 infection and should be interpreted in the context of other clinical factors. The mechanism by which the IL28B genotype mediates pegylated interferon/ribavirin treatment response in HCV genotype 1 is not yet understood and is the subject of intense research. The impact of the IL28B polymorphism on response rates in HCV genotypes other than genotype 1 is still being investigated."

The Genome-wide association studies have identified a single nucleotide polymorphism (SNP) (rs12979860) upstream of the IL28B gene, which is associated with higher sustained viral response rates to pegylated interferon/ribavirin therapy in HCV genotype 1-infected individuals so the same principal applies.

The key words in either of these tests is " ONLY ONE OF MANY FACTORS that can influence response rates to pegylated interferon/ribavirin therapy in HCV genotype 1 infection and should be interpreted in the context of other clinical factors".

Trinity

[FlGuy]

That's why the reason must be DIET until the melatonin study is complele which, no doubt, will prove that melatonin inhibits all antiviral properties of combo treatment.

[Trinity4]

Thanks, FlGuy,  I'm awaiting the results of the Melatonin study with baited breath.

[willing]

Congratulations - looks very promising! However per the fine-print warnings Trin points out, there's nothing like a PI-less lead-in of 4w or better to see what ifn response mileage you're actually seeing vs. what's advertised.

[SusieS2010]

"(Lifted directly from Susie's site without permission. Sorry Susie, I was getting the PegAssist and Commitment to Care phone #s through your homepage because they're so darn accessible there. My compliments to DayLilly.)) "

Desrt, you can copy anything you want any time. I NEVER have a problem with that. Information is to share.

I've never had the IL28B test as I'm not sure it was even available for my last treatment in 2007. I wonder if it would be necessary for me now. I can't imagine mine would come out good as I've failed every single therapy even with high dose daily interferon etc., etc. My dilema right now is whether to try telaprevir or wait for 18 mo9nths until the clinical trials of 3 drugs including ribavirin but no interferon. Many of the researchers feel that it is likely that interferon will go but ribavirin is too important. Go figure??

[SusieS2010]

BTW, the study I have from AASLD says that IL28B predicts response in 80% of people. In 20% the test isn't predictive.

[merryBe]

Trinity,
First, The original threads regarding IL28b all contained references to the studies, and the fact that it was not the only issue and that it was only given an 85% accuracy was stated several times.

Therefore it’s hard to understand how anyone would assume it’s anything more than a predictive, and not entirely reliable at that percentile. If anyone read into anything that IL28b is the "end all" of whether success is possible I would have to say it was based on a less than thorough understanding of what was being offered.

That said, the tests I just took are even more predictive only because there are now 2 genes they are offering the test for, and a third on may be offered soon as 3 sequences have been discovered. As they find out more of the chemistry, we will be able to know with a much higher degree of accuracy whether our interlukins will aid us in this struggle or not.  My hope, is the day will come that they will use the genetic blueprint as a guide to formulae that are patient specific, meaning more perhaps of INF3, or a or b will go to one patient than another, dependant on their need for extra due to their genetics.
Better still, we won’t treat anyone with INF whose body won’t work with it, we will find other triple combos that will help them to overcome and not poison them when they have a 1% chance of the INF helping. But who knows.

Is there a perfect correlation between genetics and outcomes, no. But the truth is that the chances of SVR are 2 to 3 times greater with the right genes, and that much less with the wrong genes. That means that tailoring the treatment to the patient just became hugely more important.

What that means is that the right genes give you a much higher than the original 50% predictive chance of clearance and the wrong genes…well look, the studies and threads are there for anyone who cares to examine them.

If we ignore or are dismissive of such advances in science to our own detrement IMHO.
I personally will still strive for the PI to be added, due to fibrosis I think it's my only option.
Were it not for that, and my IR I might be comfortable without the PI, but at this point, with three years lost to treatment and recovery and staring down a whole new round, it would be foolish for me to not go nuclear and avail myslef of every last snipet of advantage.

Secondly, there has been an enormous amount of work done on Insulin resistance and treatment outcome.  Both Cowriter and myself brought in literally dozens of studies showing those correlations. Clinics have told patients for many years now that diabetes makes the chances less of SVR, they know the rate of clearance is at least 10% less, but it may go higher since so many treat with undiagnosed IR.
I have to say it was hugely disappointing to see both HR, a doctor and world class hcv researcher and Cowriter, a trainer diebetic (diabetic) nurse seldom visit this board due to the cold receptions and accusatory tones that greeted them here.
While I undersatnd and aplaude healthy scepticism I think it's important to access things in the spirit they are offered and not to jump to soon to conclusions on any new information, regardless of whether we know or are already intimate with the messenger.

It might behove some members to check out the bulk of Cowriters work which still is ongoing on another site hepcnomads.com, and viewing her Insulin Resistance threads.
The insulin canceling out interferon is a big part of why people don’t SVR, and may also go a long way in explaining why some folks have such gargantuan viral loads.
The interferon is said to represent a huge part of the equation.
Natural Interferon is why 15-20% of patients clear this virus on their own, so anything that destroys our interferon needs to be addressed and I would strongly suggest everyone familiarize themselves with CoWriters work as it may make difference between succeeding or failing treatment.
It certainly plays a part, as does compliance, as does fibrosis, your genes, yada yada yada
Fibrosis is another issue where we very seldom discuss anymore due to the cold reception, but where HR has been tremendously valuable as a resource, and people are seeing reversals in fibrosis who are using his regimes, and the labs and scans prove that, and I've seen the labs.

When you stop to think about it it makes perfect sense that the HCV is actually the cause of IR and other endocrine system metabolic syndromes, or at least, part of the cause.
My diet has been healthy, whole grains, lots of veggies for 40 plus years, heck I raised my own chickens and honey bees for umpteen years, and still grow my own veggies.
So why do I think so?  Because with this virus I began to gain weight in spite of no changes in activity level or caloric intake and a relatively low sugar intake. Because the higher your interferon goes to fight the virus the higher the level of insulin you must produce to compensate for what is destroyed by the high INF level, and the more insulin you pump in the more your cells become insulin resistant, and the more that happens the more adipose tissue storage changes, and the other glandular secretions all go haywire under the constant onslaught of infection. It’s a vicious cascade.
I remember that with 2 years of my transfusion I noticed the hump on the back of my neck and thought, where did THAT come from??  Turns out, it comes from HCV and HIV both…the body begins to retain and store lipids differently, it alters metabolism to try and fight the virus, and the virus adapts continually as well. Retro viruses are very smart critters and we need to avail ourselves of every new discovery if we are ever to defeat them.

I agree, nothing can assure outcome, no adjunct is a guarantee.
And no, I'm not a doctor, I was a physical therapist, I did work with doctors for 20 years and I did teach anatomy. Would you mind sharing your background??

Can I prove IR is a valid part of the equation?  Cowriter offered a dozen studies, still on her jounal, far more in her new forum home, how much proof do you need??
I offered up half a dozen studies on metabolic syndrome being common in HCV patients,
the trouble with proofs Trin, is a lot of folks don't read them, they just make comments like "there's no proof" even when proofs are offered.
We are never going to get to 100% proofs on any topic because the science keeps changing and improving, and that means that what is very compelling now may not be as compelling down the road, but where we do agree is that we need to follow the science.

Disclaimer should be that the science is evolving, and what they think works might not.
It might be wrong. It might be that way with the Purine issue, at first we were told to EAT protein in every meal, now it looks like that could be bad with Riba, and, it could be someone will come along and disprove the whole thing  in another year or 2....the best any of us can do is to try to ferret out what is true based on the scientific method.
Methodology has a great deal to do with the reliability of any test or study, as we saw with PCR, but we must be able to access method to know if it's valid.

mb

[merryBe]

I'll have to check and see what milk purine content is, maybe it's not that high, milk is mostly water so it's not a volumous amount, unlike meat which is solid protein and much higher.

good question re: HGH !!

Well, there is reason to believe it may have not helped me in that one regard. It raised my blood sugars by an average of 10-20 points.  That may not sound like much, and at the time according to several doctors, I need not worry.
Remember at the time I brought that research in to the board no one had even whispered the word Insulin Resistance, and my pituitary function was 20% of normal, many HCV patients have had the virus effect their endocrine systems adversely.
Until I saw the new research Cowriter brought in and saw the strong correlation between even a slight elevation (only 10 pts.) and a marked decrease inSVR it would have been a hard sell.
Once I saw the research, I got my HOMA done, and found out she was accurate there as well, the A1C was not reflecting my true degree of IR due to the low HGB throwing that test off.
Once I saw this, I immediately changed my program, added first metformin, then switched to byetta and finally to victoza, but alas this was not discovered until I was in the last couple months of treatment, not soon enough to make the difference.

So to answer the question, I would probably allow my pituitary function to be low if I could not control the IR by other means. If I can keep my IR abated to say in the 80-90 range, fasting rate, then I would continue the HGH because my function is 10% of normal without it, and you need growth hormone to repair tissue, but if I cannot get into the range that I think makes sense then I will definitely dial back the HGH and take those deficiency issues while treating. In fact I’ve already played with the HGH the last 2 months just to see if I can get the BS to move, but it only grants me about a 10-20 pt advantage, and that's at zero, I got about a 10 point decrease at half dose... and so alone deleting the drug will not be a solve for my IR issues because it wasn't raising them that much, remember I only went to therapeutic dosage for my age to begin with, so not a large dosage.

It could be that once I add the ALA and some other adjuncts back that that will change,
some adjuncts are known to aide in keeping IR at bay particularly Omega 3, ala etc. Lipids do effect BS levels that been known for 20 years.

However I stopped all adjuncts when the kidney stones showed up. Kidney stones were undoubtedly due to the parathyroid tumor, but many adjuncts are all bound with dolomite or some such calcium product, bone meal, whatever,  and ergo contraindicated until I got my calcium levels to equalize and gave those stones time to resolve.

I'm not sure stopping the fats was needful, I only did that to wait on the labs coming back for stones, to see what they were, they can have various composition and until I knew I just stopped everything.  The stone were mainly from the parathyroid pulling calcium out of my bones, and even lipids effect calcium metabolism you see...in fact I think the fact that they forced me to take vitamin D with the tumor is why I got the stones, based on Dr. Norman's work.

Anyway, I'm sure this will all get resolved by the time the PI gets here. I even think now that the byetta/victoza may have been how I got the thyroid tumor.  I was told it was safer, closer to the bodies own metabolic process etc. It was side effect free, unlike the oral IR drugs, but it had a higher rate of thyroid tumors. Of course, one always thinks they won't get the worst side effect.....rolleyes...lucky me I guess.
In any case, I will probably try the Pig when this time around and hopefully at long last will maybe get a good fit.
You may remember I had bad issues with metformin, gastro but chiefly bad headaches.
My brain has issues so who knows why, but metformin had me down for the count every time I took it, and everytime I went back to it (3 times)...so it's not as easy to find good drugs for IR as folks think. (avandia, yikes)

Anyway, bottom line is, it's all a crap shoot I guess, best I can do is to try to go to good docs, keep abreast, and regroup when need be.

I've racked my brain trying to figure out if the IR or the fibrosis was the culprit here, and of the two I think I'm as if not more concerned about the fibrosis.
Doc did a visual during surgery and said far worse than biopsy indicated.
The lipid part of the equation, and the fact that virons making intracellular jumps, not using the normal route to move around has me worried. I'm wondering if they are adaptive enough to sometimes penetrate the membrane and immigrate illegally so to speak, then the case for them being imbedded in fibrotic tissues grows stronger. I think the issue becomes whether the riba or anything else will be able to penetrate where the virons may be able to. The denser the material they imbed themselves in the more chance they can remain there unscathed in my mind. How else do you explain the fibrosis equation, why should some gristle make the difference if not for this factor. Let's call it "the three little pigs factor" ....the guy in the brick house might survive when the wolf blows.

anyway, enough of my yattering.

mb

[Trinity4]

My eyes are glazed and I can't wrap head around all the "yattering".  

I wish you the best Merrybe.  May we both acheive SVR with whatever way we approach we approach or next treatment.

IR or no IR, IL28B, or no IL28B and so on and so forth.  I will continue to eat my dead chickens, fish and occasional beef with no worry of my diet inhibiting chances of SVR.  Who knows, with your proposed diet you may end up lean and mean like me. :)

Trinity

[foofighter]

2010 Dec;17

Pegylated interferon plus optimized weight-based ribavirin dosing negate the influence of weight and body mass index on early viral kinetics and sustained virological response in chronic hepatitis C

CONCLUSIONS: RVR is the strongest predictor of SVR. Early viral kinetics is not influenced by body weight or BMI when weight-based ribavirin is prescribed.

http://www.ncbi.nlm.nih.gov/pubmed/20196800

[merryBe]

foof,

I agree, in fact I think the fat tissue is more permeable than the fibrotic tissue, but it's not weight as much as the IR, which can happen at ANY BMI....it's the virus that leads to the IR not strictly the weight, however it's also how the virus dials down the endocrine system that results in slow metabolic rate which in turn cause BMI increases.

Also take note, the riba being weight based is a compensatory that may not always work.
Example: everyone assumes it is the presense of fat that cause riba to absorb, but it may be that it is the presense of concentrated bile as well, which of course help break everything down. It takes more bile to breakdown fats so they will absorb, so when you eat fat, you help the riba as well, but which mechanism is helping the riba the most becomes the question. Since most of the new drugs they are working on to get the riba to absorb are acids of some sort, some are not, it just got me thinking that maybe the acids, stomach acids, and the bile, well, it's all working together to increase riba absorption....for all we know the various jillion critters in your guts are also contributing.

Bottom line is that the BMI is not the problem but the amount of riba that absorbs is, and plasma levels can vary greatly between people, regardless of them taking the same dose and being the same weight, which means absorption is the BIG issue, not being big.

trin,
OK chicken lady, you say tomturkey, I'll say tomatoe, but I hope for your sake I'm wrong. I could not bring myself to take that risk based on the studies I found.

forgive me, but I'll keep searching for things to unravel the relaspe dilemna, and maybe one day you'll find something helpful. : )

[willbb]

Yikes!!

[Trinity4]

This was provided by Hector on another IL28B thread but it ties in quite nicely to this thread as well.  Silly researchers, they keep mentioning high BMI as a negative factor in responding favorably to treatment.  I wonder why that is?

From American Journal of Gastroenterology
http://www.nature.com/ajg/journal/v106/n1/full/ajg2010370a.html

[desrt]

So neither of you gals is even interested in trying the modified insulin pump full of non-pegylated IFN from the link I posted?

"Background: The pegylation of interferon (IFN) improved the pharmacokinetic profile with higher sustained virological response (SVR) rates in naïve chronic HCV patients compared to standard IFN. However, the SVR rates remain low in patients who experienced a previous failure to therapy (in the 8-12% range). We hypothesized that continuous delivery via an external pump of high doses of IFN may improve the SVR rates in previous non-responders. Recently, single nucleotide polymorphisms (SNP) in the IL28B region have been shown to correlate with the response to IFN/ribavirin therapy in HCV patients naïve to IFN. We now present the first analysis of the IL28B genotype in a cohort of patients who were classified as previous nonresponders to treatment.

Method: In this study, we delivered IFN-alfa-2b continuously via subcutaneous infusion using a modified insulin pump (Medtronic Minimed). Thirty subjects were randomly assigned to receive a daily dose of 6, 9 or 12 MU IFN combined with weight-based ribavirin. Viral kinetics was measured at baseline, weekly until week 4, and then at week 8, 12, 24 and 48 weeks. The “Duke” SNP rs12979860 was determined using competitive allele-specific PCR genotyping.

Results: In this cohort 20 patients had IL28B genotype CT, 3 patients had genotype CC and 6 patients had genotype TT. In 1 patient genotype determination failed. In our study there were differences among the CC, CT and TT groups with respect to viral decay at week 4, which was independent of the IFN-dose. CC subjects had an average viral decay of 2.9 log at 4 weeks, while CT subjects showed a 1.65 log reduction and TT subject showed a 1.25 log reduction (p=0.119). Of the 6 TT subjects however, only 2 subjects showed more than 1 log reduction at 4 weeks. More importantly, in the high dose group receiving 12 MU IFN/day, all 10 patients had more than 2 logs viral decay at week 4 of treatment regardless of their IL28B genotype. Of all 30 patients 6 achieved SVR, 2 in the CC group (one in each of the 6 and 9 MU group) and 4 subjects in the CT group, who all received 12 MU IFN/day. In the multivariate linear regression analysis both IL28B (p=0.036) and IFN dose (p=0.002) were significantly associated with viral decay at week 4.

Conclusion: These results show that the IL28B genotype can be a strong predictor of both viral decay rates and subsequent SVR. Moreover, high doses of IFN can potentially overcome the innate lack of IFN sensitivity that the IL28B naïve data predicts. Finally, these results also support the concept that continuous delivery of IFN in previous therapy failures can be a successful treatment strategy, especially those with CT and CC genotypes."


Sheesh, where's your sense of adventure?

[desrt]

"...I bet i was a TT which is why it took so long for me..."
And I bet I have at least one C allele which is why I cleared with less than 24. But unless we get the test done we're still just guessing. I'm considering scraping together the $300 and having the test done, not just for my own curiousity, but because I think that those of us who are SVR could create a valuable data base. It would give our tx experiences some context.

[nygirl7]

I agree with you desrt that is what I was thinking too.

[BeatTheBeast]

Hi, merryBe,

I have been reading posts here for a while and just posted my first query in a new thread, re whether Quest tests for both rs associated with the IL28B gene.  I probably should have posted that query in this thread instead of starting a new thread.

Also, I was very interested in your comments about IR.  I have the impression that this topic is not on the radar screen of hepatologists but have thought it's very important for some patients.  Would it be possible for me to email or call you?

The information on this Board is terrific.  Thanks.

BTB

[nygirl7]

If you use the search feature on this forum and look up Co-Writer they are kind of the resident expert on IR, I am sure you can find all the information you could possibly read about - it has been a much discussed topic here over the years on MH.  Even though doctors might not be aware of it.......this forum is.

Good luck.

[BeatTheBeast]

Thanks for the suggestion.  Indeed a wealth of information has been posted.  I will continue to research and digest this.

BTB

[merryBe]

not ignoring you at all, just missed the post somehow.

my big confession is I do most of my reading and writing late at night or at dawn, when eyes are glazed over,

any time you think I need a heads up please PM and alert me as I love the new stuff.

Actually though, I kinda crossed the INF puzzle off my list about a year ago.

I decided then to not do the peg. I won't do standard INF either, but will shoot for the daily injections 3 times a day. Because of the short half life this makes more sense to me then every 12 hours, HL is 4 hrs. so that hardly makes sense.

Of course, the pump would be even better, assuming one doesn't mind the extra surgery to implant it, and extra risk of infection with it.
I'll have to mull it over, but since every time I'm put under is risky in stage 4 I'll probably stick with the 3 shots a day. With a good wrist watch I think it's manageable.
With 3 shots a day there will be very few windows where INF it not at optimal levels.
whereas with peg the last day or 2 of each week could be very low, and with a pump, it could fail, and you wouldn't get any if it did.  Of course, if one forgets the shots same thing, but assuming one can be compliant I thought that method most guaranteed steady state with the least risk.

Had you ever thought of that?  I mean, it only makes sense to me, although I haven't even run it by my doc yet.  He may think its too hard, but I can always do it that way regardless. It's not hard in my world.

mb

[foofighter]

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.

[BeatTheBeast]

The Arup test for the TWO  Interleukin 28 B (IL28B)-Associated SNP Variants:is 2004680.

BTB

[nygirl7]

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!!!!!!!!!!!!!!!!!!!!!!!

[desrt]

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.

[it'sallgood]

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

[merryBe]

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.

[Trinity4]

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.

[James10500]

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.  

[merryBe]

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.

[SusieS2010]

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.

[James10500]

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.

[FlGuy]

Yeah right, daily interferon 3 times a day.  Lady Gaga wouldn't even do that if she had HCV.

[merryBe]

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

[SusieS2010]

You keep saying the inf lasts 8 hours and that is just not true with a half life of 4 hours.

[James10500]

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.

[merryBe]

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.

[nygirl7]

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 (withdrawal) 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.

[merryBe]

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.

[Trinity4]

Why you just try it yourself and see how that works for you?  Then you can report back, low purines and all.  

[merryBe]

>>>>>>>>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 (withdrawal) 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

[James10500]

What ever you decide to do I hope it works for you.  That's the important thing.  Best of luck to you!

[merryBe]

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??

[SusieS2010]

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.

[merryBe]

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.