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233616 tn?1312790796

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.
51 Responses
979080 tn?1323437239
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.



Avatar universal
"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
148588 tn?1465782409
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.))
Avatar universal
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

96938 tn?1189803458
"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.
Avatar universal
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
179856 tn?1333550962
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......)
Avatar universal
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







96938 tn?1189803458
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.
Avatar universal
Thanks, FlGuy,  I'm awaiting the results of the Melatonin study with baited breath.
Avatar universal
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.
Avatar universal
"(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??
Avatar universal
BTW, the study I have from AASLD says that IL28B predicts response in 80% of people. In 20% the test isn't predictive.
233616 tn?1312790796
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 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
233616 tn?1312790796
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


Avatar universal
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

Avatar universal
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
233616 tn?1312790796
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. : )
Avatar universal


Yikes!!
Avatar universal
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

148588 tn?1465782409
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?

148588 tn?1465782409
"...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.
179856 tn?1333550962
I agree with you desrt that is what I was thinking too.
Avatar universal
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
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