Hi again,

Thanks for explaining that. What trial name was assigned to your group? I hadn't seen mention of that use of Bocepreviir before. I started it after week 4 and did a total of 28 weeks. I never was tested for the il28b gene and even though I've achieved SVR, my curiousity is getting the best of me. 

I also agree with the new DAA's, we will see an ever decreasing use of the Protease Inhibitors. But you're right, there will continue to be a big market, particularly in the third world regions and those governments that are slow to find financing (support)of these new, grossly expensive wonder drugs. 

I wish you the best of luck on your EOT 52 tests, I'm right behind you. I think the future is looking pretty good for all of us! Be well!

Tig

Hi Tig,

thanks for the welcome!  I found this forum very late on during my treatment and as I was already involved in two, I decided not to start posting on another, even though I often read the posts on this one and think it's a great site. 

OK so my trial:  It was for those with the IL28bCC gene.  In the arm of the trial that I was on, if you achieved RVR on the lead in (i.e. Not Detected at 4 weeks), you continued on PEG-IFN/RBV only for a total of 24 weeks.  If you didn't (and as you can see from the signature line that I did not), then you had to add in boceprevir.  However, they allowed a two week turnaround for lab results (even though they usually came in within a few days).  This meant that those who achieved RVR in my arm only did 24 weeks dual in total but if you did not (like me) you added in boceprevir at the beginning of week 7 (i.e. 6 weeks on dual + 24 weeks on triple = 30 weeks).  On the other arms of the trial, whether you got RVR or not, you added in boceprevir at week 5.  If you were found to have had an RVR, you did a total of 24 weeks (i.e. 4 weeks dual, 20 weeks triple) and if you were not, it was an RGT approach.

Yes, I got SVR24 ... but just now waiting on my one year test.  My doc says it's durable in about 99.3% of cases .... doesn't stop me being terribly anxious and worrying endlessly about my ongoing liver twinges ...

Kind regards.

SRS

PS:  I think with all the new drugs, it's all over for boceprevir although maybe Merck will use it in other markets other than the US, UK etc. (and so the data will be useful).  I noticed (but last year) they were going to do trials for 16 weeks in Asia (where very high percentages of the population will have the CC allele - 90% I think).

-- Edited by SRS on Sunday 5th of October 2014 07:18:21 PM

-- Edited by SRS on Sunday 5th of October 2014 07:19:07 PM

-- Edited by SRS on Sunday 5th of October 2014 07:19:46 PM

Hello SRS,

Welcome to the forum and thank you for providing that explanation. I see you completed treatment a year ago this month, congratulations! I hope that means you have achieved SVR along the way. Please let us know a little more about you if you should choose. I'm curious why they delayed your Boc introduction until week 7 of your trial? Any specifics are interesting and appreciated. Thanks again for sharing your story! Good luck...

Tig

Hi

I am fortunate enough to have the favourable CC allele at RS12979860, so when I found this out, I did quite a bit of (scholarly) reading about it (powered by google of course).  I can find the research and post links if anyone is interested.

I suspect the reason that it's more common to be tested for the CC, CT or TT allele at RS12979860 is because it is almost always the case that if you have the CC allele, then you also have the favourable TT allele at RS8099917.  I was tested for both and have both and I know others where this is also the case.  However, if you have TT at RS8099917, you do not always have CC at RS12979860.

It's also the case that those with the CC allele are more likely to resolve their HCV spontaneously when they first become infected, especially if they have G1 and are female.  This obviously didn't work for me!  I think that accounts for the fact that they are smaller numbers of those with HCV and the CC allele (than with CT or TT), but I'm not sure about this.

SRS

-- Edited by SRS on Sunday 5th of October 2014 06:17:19 PM

-- Edited by SRS on Sunday 5th of October 2014 06:18:04 PM

Thanks for the additional information! It would certainly be interesting to know some of this genetic history. It's amazing what they can determine from a little saliva!

Tig

Tig,

Oh my God yes! But unfortunately, they have now removed the health interpretation BUT the raw data DNA file is still available for your interpretation. You can download the entire DNA file if you like. I found out deep dark hidden secrets about my ancestral past that I would have never ever dreamed of. I have light brown hair (with a little gray now--ha ha) and fair skin with blue eyes, but when I clicked on my paternal haplogroup (The Y chromosome) it led me straight to Africa. A male's Y chromosome never changes unlike the general genetics of a person that result from interracial encounters. After extensive research, I found out that my 10th great paternal grandfather was African and my 10th great grandmother was a Nansemond Indian. From that point on, all of my ancestors were Caucasian and that secret was buried in the past many, many generations ago.

I was one of the last ones to receive the health report before the FDA blocked that aspect of it. It was all politically motivated with the big pharma behind the effort according to the chatter on the 23andme site. 

I have found and verified relatives that I did not know existed and found out a plethora of health information. Best $99 that I have ever spent.

I've read about this test and recall the FDA involvement that changed access to some health information previously provided by it. In your opinion, is this something worth pursuing? I have found some coupons available that offer significant cost savings. 

Tig

Very interesting Malcolm. I have an account with 23andme and so I searched my raw DNA data and found these results:

rs12979860 "no call"
rs8099917 GT
rs12980275 AG

But since I'm on the S/O treatment maybe it will not matter as much.

Hi John, I`m glad you`re going to look for a new doctor, you should be getting much better advice and information, and it must be very frustrating for you when you aren`t getting reliable answers.  We`re very lucky to have Malcolm here with his wealth of knowledge but this isn`t a medical forum and shouldn`t be used as a substitute for the proper medical attention you should be getting. 

Good luck with finding a more knowledgeable doctor, this is your health and you deserve better treatment!

ps - In future, would you mind starting a new thread in the `General Discussion` area, please John?  Thanks. ~ Jill

John,

ALP is Alkaline phosphatase. It is more a test of liver function than the enzymes (GGT, AST and ALT).  Cirrhotics often have a slightly elevated ALP as some of the regenerative nodules don't have proper bile drainage networks.  ALP has high concentration in the cells lining the bile ducts, so any blockage of bile will cause ALP to go higher. Try to find someone to answer your questions and keep a close watch on the ALP and AFP.       Good luck.

You are right about seeking out new doctor - I was ahead of you on that - today she said that was a non specific test and the fact that the bilirubin went down is no cause of concern.  I know I have cirrhosis - she hasn't called it that yet.  Good advice my man!

By the way it is Alkaline phosphatase this time - last month was the rising alpha feta protein.

Hi John,

You asked about rising ALP levels last month. Your doctor should be answering these questions. If she doesn't, I'd change her. You posted that she discussed Rx for HCC after an MRI report suggested a benign lesion. To me, that doesn't indicate a caring, informed individual.  Rising ALP levels are always a cause for concern, and you should demand some answers. Your posts indicate that you have cirrhosis, but you and your doctor don't seem to accept this. I would demand a biopsy or Fibroscan, and this will indicate whether you need to seek out a new Rx fairly urgently. Up to you buddy.

Just got the final blood tests for the 6 months of waiting. Bilirubin, AST and alt all came down but alp is rising quite quickly.  Iti was 100 in january and now is 190.  A new high for me by far.  Is this just one of the hep fluctuations thing?

Hi guys,

I think we're getting a bit mixed up with our genes.

The ITPA gene is located on chromosome 20 and has SNP's called rs1127354 , rs7270101 and rs6051702. Only the first two have been studied in detail. Patients may have CC (most common ~70%), CA or AA alleles at rs1127354, and AA(all Japanese patients), CA or CC alleles at rs7270101. This gene is only for prediction of the likelihood of Ribavirin-induced anaemia, and has no relationship to RVR or SVR.  Patients with the CC, AA at these SNP's are more likely to develop anaemia in the early stages of Rx, and may need Riba reduction or Procrit. This may be slightly useful but I cannot see how it would affect the decision of whether to have Rx.

The Interleukin 28B gene is located on chromosome 19, and predicts likelihood of response to Interferon-based Rx.  It has been discussed in detail, and the SNP's rs12979860 and rs8099917 are both important. In Japan and China, only rs8099917 is done routinely.  Having the CC, TT alleles at these SNP's is a powerful predictor of Interferon response and will remain so, as long as Interferon is used with the DAA's.  With Interferon-free Rx's, it is uncertain whether it will remain useful.  If an NS5A blocker is used, it should have no influence.  My doc has always thought the rs8099917 SNP is important for Australians, and was confident I'd do well, as I am TT at this site, although CT at the other.

Genetic variations between different nationalities should always be considered when reading articles from non-USA sources.

Matt Chris wrote:

---

Hello Rebeca

The Gene testing company 23andMe under the drug response section it reads this.

A common side effect of ribavirin(RBV)-based therapy is anemia, which is a reduction in the number of red blood cells in circulation. Because red blood cells are necessary to transport oxygen to the tissues of the body, anemia can cause dizziness and fatigue. In this study, researchers compared 231 individuals who experienced anemia while being treated with pegylated-interferon/ribavirin (PEG-IFN/RBV) for hepatitis C to 463 individuals who were treated but did not experience anemia, all of Japanese descent. They found that individuals with the AA or AC genotype at rs1127354 in the ITPA gene had about 33 times lower odds of having anemia in response to PEG-IFN/RBV therapy, compared to individuals with the CC genotype. Similarly, another study in Europeans found that those with the AA or AC genotypes at rs1127354 maintained stable levels of hemoglobinthe oxygen-carrying component in red blood cellswhile taking PEG-IFN/RBV, while those with the CC genotype experienced a decrease in hemoglobin levels. Low hemoglobin levels are an indicator of anemia.t

It looks like it does not refer to the SNP rs8099917 so will have to do further research.

matt 

 

---

 Thank you Matt, very interesting.

If you get more information please let me know, or tell me where I can find.

Big hug

Hello Rebeca

The Gene testing company 23andMe under the drug response section it reads this.

A common side effect of ribavirin(RBV)-based therapy is anemia, which is a reduction in the number of red blood cells in circulation. Because red blood cells are necessary to transport oxygen to the tissues of the body, anemia can cause dizziness and fatigue. In this study, researchers compared 231 individuals who experienced anemia while being treated with pegylated-interferon/ribavirin (PEG-IFN/RBV) for hepatitis C to 463 individuals who were treated but did not experience anemia, all of Japanese descent. They found that individuals with the AA or AC genotype at rs1127354 in the ITPA gene had about 33 times lower odds of having anemia in response to PEG-IFN/RBV therapy, compared to individuals with the CC genotype. Similarly, another study in Europeans found that those with the AA or AC genotypes at rs1127354 maintained stable levels of hemoglobinthe oxygen-carrying component in red blood cellswhile taking PEG-IFN/RBV, while those with the CC genotype experienced a decrease in hemoglobin levels. Low hemoglobin levels are an indicator of anemia.t

It looks like it does not refer to the SNP rs8099917 so will have to do further research.

matt 

Matt Chris wrote:

---

Thanks Malcolm for brining this topic up, I recently read a article by  

Lucinda K. Porter, RN

 HEALTHWISE: Hepatitis C and Your DNA  from HCV  advocate newsletter 

 

This is a small excerpt from the article regarding the importance of genetic testing for HCV  treatment

 

If you were a geneticist and had never met me, youd know that my eyes are blue, my hair is straight, and that I can tolerate lactose. If you knew I had hepatitis C and had been through interferon-based treatment twice, you could look at my DNA, and despite not knowing my hepatitis C genotype, you would guess that I didnt respond to treatment. You might also predict that my platelets would drop dramatically from interferon, and that my odds of developing ribavirin-induced anemia are typical.  You would be right on all accounts.

Your genome knows much more about your medical history than you do, said scientist Danny Hillis. Many of us who live with chronic hepatitis C virus infection (HCV) can tell you what our HCV genotype is, liver disease stage, and viral load, but when it comes to knowledge about our own DNA, we draw a blank. Isnt DNA testing for paternity suits and TV crime shows?

Actually, any adult can have genetic testing, and you dont need a doctors order to have it done. Many genetic testing companies offer a wide range of services, and I chose 23andMe. I received a lengthy report on potential health risks, ancestry, traits, and drug-response information.  It cost me $99 ($79 for additional kits) and some saliva. I had the results in less than six weeks.

I did this because I wanted the drug-response information. Generally, we look at factors such as HCV genotype, HIV status and presence of cirrhosis when trying to predict response to HCV treatment. However, each of us carries another predictor of response to medication, and this information is located in our genes.

From what we learned from Malcolm's post and this article we understand the importance of knowing this Genetic information when we are considering using interferon and possible other drugs in the future.

 

If you want to learn more about genetics follow the link in the article (23andMe) it help me immensely.

 

Matt 

---

Hi  Matt

I´ve read  in one of your post that you received a report about genetic in 23andme. Do you receive in that one, the gene that is a predictor of response to treatment of HCV ?

My doctor ask for  IL28B, but not another  (The SNP rs8099917) Mallani explained about that.

Thank you.

Hi Matt,

Interferon is a bloody good drug, particularly in the Peg. form. It's a shame it has so many Sx, and that some patients are not interferon sensitive. the IL28B test will give a good indication of your interferon sensitivity. It is effective against all Genotypes and mutations are not a factor. It will be around for years to come.

Miravirsen is not really gene related. It blocks a liver hepatocyte molecule called miR-122, which is a microRNA helper, enabling the virus to replicate. This is different from the DAA's that act directly on viral sites. Supposedly, Miravirsen should be effective against all Genotypes and mutations. It's into early Phase 2 studies at the moment, so we'll have to wait for a while. Cheers.

Malcolm and Members

As regards the 23andMe Genetic test looks like I need to investigate really what is included in its results.

I will also check with the other times I had the IL28B tests to see if there was any info on Interferon intolerance.

Malcolm from what you wrote about what your Doctor determined by having your Genetic test for your Triple therapy is seems that anyone considering Interferon would benefit by having these genetic tests to avoid unneeded painful interferon treatment. Is that the correct viewpoint?

I myself am considering possible Interferon with either triple or Quad. treatment some time in my future.

Their seems to be a lot research being done in all areas of Medicine that include Genetic based treatments.

Is not the Miravirsen RNA future HCV treament some type of gene based based therapy?

Matt 

Hi Dillo,

Thanks for the info. I wasn't sure whether the USA testing also included rs8099917. You are very lucky having CC and TT, and should do well.

Matt, I wonder what is included in Lucinda Porter's 23andMe gene test. The standard IL28B test alone costs $280 over here, so I'm not sure what you get for $99. I had a look at the site and it is not specific about what tests are done. Why don't you get it done and enlighten us? Cheers.

I find this terribly unfair, but as a genotype3, I was refused the test as the cure rate is higher than genotype 1 and 4. I have read about plenty of people with type 3 that have gone on to have fatty livers and can't cure on current meds. To be honest, type 3 is being neglected on the medicine front as we are a relatively small percentage. I am a 3b which seems to be an either further minority. I don't know if I am easier to treat than 3a, but time will tell! :)

Thanks also Malcom for bringing this up. It made me go back and look at my test. My doctors only talked me having a favorable gene for treatment.

I did go back and find the test online that I didn't have access to back then

rs12979860 Favorable Genotype: C/C

rs8099917 Favorable Genotype: T/T

I still had no idea what all this meant except what they told me. It was a factor in deciding to go ahead with treatment though. rs12980275 was not included in the test.

Matt,   I saw that article too. Interesting.

Hi Tig,

These gene tests will continue to be accurate. Here in Australia, this is one of the first tests ordered when Rx is contemplated. The rs12980275 is considered less relevant in Australia, but can be done if requested. Time will tell whether this test remains significant for the new DAA's, but as interferon will continue to be used in most countries for many years to come, I can't understand why this test is not done routinely, and why there is only interest in only one of the SNP's. If my results were TT, GG and GG for all 3 SNP's, there's no way that I would consider interferon Rx. Note that this test only applies to those with Genotype 1.

This test is far more important than testing for ITPA gene polymorphisms. This may give an idea of possible Hb response during Rx, but so what. Hb reduction can be managed, but interferon response can not. Cheers.

If you have begun treatment or previously had unsuccessful treatment in the past, will these gene tests continue to be accurate? I was never given the opportunity or information about this test previously. It certainly would've been nice to know prior to making the decisions made. Thanks for the info!

Hi all,

You may have heard about the Interleukin 28B ( IL28B) gene test. It is used as a predictor of response to treatment, particularly with interferon based regimes. The usual comments are that those with the CC allele do better than those with the CT or TT alleles.

This is only partly true. There are 3 SNP's( single nucleotide polymorphisms) near the IL28B gene.  The one commonly quoted is the rs12979860 SNP. It is quite correct to say that the CC allele has a better chance of SVR than the CT and TT alleles. (70%, 35%, 20%).  However this is only a part of the story . There are 2 other SNP's that are just as important. The SNP rs8099917 has alleles called TT, GT and GG.  This is probably more important than the previous SNP.  Chances of SVR are: TT-80%, GT 15%, GG 0-5%.  The other SNP is called rs12980275. The alleles are AA, AG and GG. Chances of SVR are: AA-45%, AG-45%, GG-10%. All 3 SNP's should be considered when giving advice to patients.

In Australia, if you are sent for an IL28B test, you will receive results for both rs12979860 and rs8099917. I have been tested twice with the same results- the last test was in 2011. My results were CT for  rs12979860 and TT for rs8099917. This is one of the reasons my Hepatologist was confident that I'd do well. These gene tests are useful for Interferon-based treatments, and may be less important with the newer DAA's. The viral site NS-5A contains an interferon-modulating protein, so if this site is blocked, interferon may be more effective.

Sorry for this technical post, but patients are not being given the full information when they are just told they are CC, CT or TT.