It just got real......

[dooklebug]

I just received my genotype results.  I know I'm G1, but I don't understand the rest.  I've copied and pasted them here.  Can someone help?  All I'm seeing is the stuff that sounds bad.

IL28B Polymorphism CT
IL28B Interpretation (Note)
IL28B-related rs12979860 CT genotype has been associated
with a poorer viral response in HCV genotype 1-infected
individuals treated with combined pegylated-interferon and
ribavirin therapy as compared to CC genotypes. Individuals
with the CC genotype, which is not the situation for this
patient, have approximately a 2- to 3-fold greater rate of
sustained virologic response (SVR) in HCV genotype
1-infected individuals treated with combined pegylated
interferon and ribavirin therapy as compared to either the
CT or TT genotypes. Similar SVR have been observed across
various racial groups including European Americans, African
Americans, and Hispanics. CC genotype has also been
associated with a 3-fold increase in rate of spontaneous
clearance of HCV. IL28B genotype is only one of many
factors that can influence response related to pegylated
interferon/ribavirin combination therapy in HCV genotype 1
infection and should be interpreted in the context of other
clinical factors.
Direct polymorphism analysis of the IL28B-related
rs12979860 polymorphism is performed by a Polymerase Chain
Reaction (PCR) based 5'-nuclease assay using fluorescently
labeled detection probes. This DNA testing will not detect
all the known mutations and polymorphisms of IL28B.
Absence of mention of a specific gene mutation or
polymorphism does not rule out the possibility that a
patient has that or another variation that can impact the
function of this gene, drug response or drug side effects.
Laboratory developed test.

Thanks in advance for your help.

[dooklebug]

These are all the blood tests my hepa ordered at my first appointment.  The only one that hasn't come in yet is the genotype:


Order Name Type
COMPREHENSIVE METABOLIC PANEL Lab
PROTHROMBIN TIME(PT/INR) Lab
HEPATITIS A ANTIBODY,TOTAL Lab
HEPATITIS B CORE ANTIBODY,TOTAL Lab
HEPATITIS C GENOTYPE Lab
HCV RNA BY PCR, QUANTITATIVE Lab
ALPHA-FETOPROTEIN TUMOR MARKER Lab
INTERLEUKIN 28B POLYMORPHISM Lab

[Idyllic]

Hey ~ I caught the fact that your biopsy was in the mail :)
I am impressed you got them to do that while your doctor is away. I had my fist biopsy during the holidays it was grueling waiting for the results.

If you look at your 16 Dec labs again does it say "With Reflex to Genotyping"?  The reason I am a little confused is I am thinking why have a PCR less than two weeks apart unless it is to ***** your Genotype?

In November you tested for the Antibody

03 December you confirmed presence of the virus with a viral load of 5960

16 December you posted HCR RNA PCR QT RSLT with a VL of 6900 (for labs done on 12 Dec).
_______________

I looked at my old labs and (for LabCorp) on my subtyping it has two sections.

1) HCV RNA PCR  expressed in IU/mL and in Log10
2) HCV Genotyping Non Reflex 1a

_______________
The LabCorp test to differentiate between HCV subtypes 1a and 1b is CPT Code 87902. It is called Hepatitis C Virus (HCV) Genotyping, Nonreflex.
It is this:
http://tinyurl.com/a5dm3yt

I think Quest automatically reflex tests above a certain detection limit.

[dooklebug]

I don't think I was very clear in my post.  I do have copies of all the test results that have come in, except the liver biopsy which was performed by the general surgeon who did my appendectomy at the same time.  His nurse is the one I spoke with yesterday and she didn't want to give me any information she wasn't clear on.  She is mailing me the results.  In retrospect, I should have asked her if there was anything mentioning fibrosis/cirrhosis.  She probably could have told me something then.  

UTSW (where my hepa practices/teaches) has a really cool online app called MyChart and they post test results, etc. as soon as they have them.  I checked today and the only result missing from the initial blood work done on 12/11 is the genotype test.  I mistakenly thought the one I got yesterday was it.

As I said earlier, I am going to have to begin practicing patience - something I'm not very good at.  :)

[pooh55811]

It appears that your doctor (or the nurse or the office team) is not giving you the printed copies of all of the lab results/test results. You need those copies.  They seem unwilling or unable to answer the questions you have and you do not have all of the paperwork to be able to look and see for yourself.

Let them know that you expect a copy of every lab result and every test result. Tell them you will come in and pick up the lab copies this week. Or they can send them (which might take them forever). Another option would be to get copies directly from the lab. Some labs are uncooperative.

Your Genotyping test should state specifically which Genotype you have. It should be very clear and not mixed in with any explanation of a test. It should clearly state something like:
Genotype     1
or
Genotype 1a
or
Genotype 2
You need to know the Genotype because your Genotype determines which drugs you will use.

It will be very helpful for you to have copies of these tests, not only for now, but also for the future.

[Advocate1955]

Try not to panic.  Your doctor's office will probably get back to you on Monday or Tuesday.  Hopefully they will send you all of your results and schedule an appointment to meet with you to discuss next steps.  Answers will be helpful when you get them from your doctor, but keep in mind that new questions always come up too.  I think you are in high gear right now because of the unknown, so just take a little bit of time to relax and calm down.  Although you may be G2 or G3, you are more likely G1, since it is the genotype most commonly found in the US.  Although G1's have a bit more difficulty attaining SVR (Sustained Viral Response = cure), many do.  Most of the new treatments that are currently in clinical studies are for G1s, so that is good to know.  Depending upon the stage of your fibrosis (stage of your liver damage), you and your doctor may decide to treat your Hep C now, or you and your doctor may decide to wait until new treatments are approved and available.  Currently, the approved treatments for G2 and G3 include two medications (Interferon and Ribavirin).  I hope I have that right, someone can correct me if I'm mistaken.  Currently, the most recently approved and most effective treatments for G1 include three medications (Interferon, Ribavirin, and either Incivek or Victrellis).  Nothing bad is going to happen today, tomorrow, or even over the next 6 months in terms of your Hep C or your liver.  Your doctor is likely to recommend that you take a vitamin without iron, drink lots of water, rest, and exercise.  If you need to lose some weight, now is a good time to try to do that (in a healthy way).  Your doctor may also recommend that you eat lots of fresh fruit and vegetables.  Until you can get your biopsy results and your genotype results, try to relax.  Nothing you do at this point is going to change the results or change the treatment plan.  Don't worry about whether the viral load is going up or going down, because it doesn't matter.  The viral load goes up and down every day, and it doesn't correlate to whether there is more or less damage to your liver.
You're doing great.  You've gotten a lot accomplished in a few short weeks.  Try to take it easy until you hear from your doctor.  There are some great websites that we can direct you to if you want to learn some more information.
Advocate1955

[dooklebug]

I am soooooo confused.  Did the above test not indicate I am G1????  I have sent a message to my hepa requesting an appointment just to discuss the results of this test and my liver biopsy.  My scheduled appointment isn't until May, but i simply cannot wait that long.  I'll go insane!!!  I know I have the very best team of docs in my area for this, but it is very frustrating waiting on a response from them.

It sounds as if they are being very thorough, since many responses I have gotten from this post indicate this particular test isn't standard.  And I appreciate it, but I NEED ANSWERS!  Hopefully, now that the holidays are over, they will be more responsive.  Patience, obviously, is not a virtue I possess.

Once again, this site has made me feel less alone.  I am ever so grateful to you and everyone else who has responded.  I cannot wait until I have reached the level of acceptance you seem to have.

[judywallace5]

Good morning my friend.  Wish I could be of more help. I didn't receive the IL-28B assay, just the genotype 2b and the viral load and the information that it was replicating very fast.  I do know that this IL-28B test helps to determine the chance for successful Hepatitis C tx but I don't think my insurance company covered this test because it is so expensive. But simply put, this IL-28B knowledge of specific genetic information about the virus and you will help your dr figure out the best Hepatitis C tx plan.  The dr can try to tailor the tx specifically to you. Wish I did know this information since my mother died of this liver disease and my sisters all have hcv.

[Idyllic]

If I am understanding things correctly so far you know your IL28B status but not your genotype or your stage of fibrosis.

Many of us walk into treatment without ever knowing our IL28B type. It is too late for me to know for certain but I am thinking being eRVR with triple would give me more confidence than knowing I had a favourable IL28B type.

Said another way some literature points out that while IL28B genotype is a strong pretreatment predictor of SVR, when the initial response to peginterferon and ribavirin was considered, RVR rather than IL28B genotype was the strongest predictor of SVR.
http://www.medscape.com/viewarticle/740029
____________________

★★Are you sure you are Genotype 1?★★
☆☆ Have you been tested since 16 December 2012?☆☆

☞ I remember you posting your initial VL info last month and there was a sentence that gave the limits of detection for that particular assay and parenthetically indicated the limit of detection for Genotype 1 was different. It seemed you might have been under the impression it meant your genotype was type 1 however hrsepwrguy pointed out it was merely a reference within the test and not your genotype☚

http://www.medhelp.org/posts/Hepatitis-C/Results-are-coming-in/show/1862441#post_8626767

_____________




It

[dooklebug]

Thank you so much.  You have no idea (or maybe you do) how much you have eased my mind.  I may sleep tonight. :)

[pooh55811]

PS: Just a further note.

That statement, "Individuals
with the CC genotype, which is not the situation for this
patient, have approximately a 2- to 3-fold greater rate of
sustained virologic response (SVR) in HCV genotype
1-infected individuals treated with combined pegylated
interferon and ribavirin therapy as compared to either the
CT or TT genotypes."

That "2-3 fold greater rate of SVR" statement refers to treatment with Interferon and Ribavirin. Adding the Protease Inhibitors (Incivek or Victrelis) has changed that ratio as you will have seen in the last article I posted. The SVR rates for CT and TT increased dramatically with the addition of either Incivek or Victrelis.

[dooklebug]

Thanks, pooh.  I will look at the link tomorrow.  I assumed this information said I am genotype 1.  I'd never heard anything about the whole CC, TT, CT thing.  This just gets more and more confusing.  But as you say, we must just move forward and treat.

The results of my liver biopsy are in as well.  The surgeon's office is mailing them to me.  All the nurse could tell me was that it confirms that I have chronic HCV and that it is "moderately active".  She didn't understand the rest of the information.  They have sent the results to my hepa, but she has been out of town and my next appointment isn't until May.  As you've probably gathered by now, I'm not the most patient person.  Guess I'll be learning a lot about that as well during this journey. :)

[pooh55811]

This is from 2011 but it gives the information on the trial data and you will see that people with the CT gene did quite well with treatment. The SVR rate for CT was 71%.

Telaprevir Improves HCV Cure Rates Regardless of IL28B Status
SUMMARY: The Vertex experimental protease inhibitor telaprevir, taken with pegylated interferon plus ribavirin, increased sustained response in people with all IL28B gene patterns, researchers reported at EASL 2011.

It is now well-established that variations in the human IL28B gene, which plays a role in interferon signaling, is a major factor in determining how well people will respond to interferon-based therapy for hepatitis C virus (HCV) infection.

Each individual inherits 2 copies of each gene, 1 from both parents. The particular location -- known as a single nucleotide polymorphism, or SNP -- associated with interferon response can have 3 patterns: CC (which predicts the best response), CT, and TT.

A growing body of research is exploring factors associated with IL28B, including response to new direct-acting antiviral agents. At the European Association for the Study of the Liver's International Liver Congress (EASL 2011) last week in Berlin, investigators with the ADVANCE and REALIZE trials reported on associations between IL28B patterns and sustained response to the experimental HCV protease inhibitor telaprevir.

Below is an edited excerpt from a press release issued by Vertex describing these retrospective genetic analyses and their findings.

Data From Phase 3 Studies Showed Substantial Improvements in SVR (Viral Cure) Rates With Telaprevir-Based Therapy Compared to Currently Available Medicines in People With Hepatitis C, Regardless of Their IL28B Genotype Status
90% of people with the 'CC' variation of IL28B who were new to treatment and received a telaprevir-based regimen achieved a viral cure, 78% of them were eligible to stop all treatment at 24 weeks.
Nearly three-fold improvement in viral cure rates was observed among people with the 'CT' and 'TT' variations compared to the control group, regardless of prior treatment experience.

Berlin -- March 31, 2011 -- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced new data from retrospective analyses that evaluated the relationship between variations at the IL28B gene and a patient's response to treatment with telaprevir in combination with pegylated interferon and ribavirin from two of its pivotal Phase 3 studies (ADVANCE and REALIZE) for a group of people who were tested for IL28B genotype.

These analyses showed that people in these studies had substantial improvements in sustained viral response (SVR, or viral cure) rates across all IL28B genotypes (CC, CT or TT) for those treated with telaprevir-based combination therapy compared to those treated with pegylated interferon and ribavirin alone.

Telaprevir is a medicine in development for the treatment of genotype 1 chronic hepatitis C. Safety and tolerability results were consistent across the Phase 3 studies of telaprevir. Data from these IL28B analyses were presented today at The International Liver Congress 2011, the 46th annual meeting of the European Association for the Study of the Liver (EASL) in Berlin, Germany.

A specific genetic region near the IL28B gene is referred to as an IL28B genotype. The three variations of IL28B genotypes have been associated with a person's response to hepatitis C treatment with pegylated interferon and ribavirin. The CC variation is associated with better responses to these medicines.

"Doctors sometimes use IL28B genotype status to decide which patients should be treated with currently available medicines because people with the CT and TT variations of IL28B tend to have substantially lower viral cure rates compared to those with the CC variation," said Ira Jacobson, MD, Chief of the Division of Gastroenterology and Hepatology at New York-Presbyterian Hospital/Weill Cornell Medical Center, and the Vincent Astor Distinguished Professor of Medicine at Weill Cornell Medical College and principal investigator for the ADVANCE study. "In this study, telaprevir was associated with a substantial improvement over currently available medicines, regardless of IL28B status, and the greatest improvement was observed in patients with the CT and TT variations."

In ADVANCE, patients were randomized 1:1:1 to receive telaprevir (eight weeks or 12 weeks) in combination with pegylated interferon and ribavirin, followed by pegylated interferon and ribavirin alone for a total of either 24 weeks or 48 weeks of treatment. Eligibility for the shorter treatment duration was based on having undetectable hepatitis C virus at weeks four and 12. Among patients in this study tested for their IL28B genotype, 90 percent (45/50) of CC patients who received a 12-week telaprevir-based combination regimen achieved a viral cure and 78 percent (39/50) of them were eligible to stop all treatment at 24 weeks. These results were compared to 64 percent (35/55) of patients who achieved a viral cure with pegylated-interferon and ribavirin alone for 48 weeks.

"The 90 percent viral cure rate among people with the CC variation of IL28B in this study is significant, but the fact that nearly 80 percent of them were eligible for the shorter course of treatment is an equally important finding," said Robert Kauffman, MD, PhD, Senior Vice President and Chief Medical Officer for Vertex. "Vertex plans to conduct a study evaluating a short-duration, 12-week telaprevir-based regimen in people who have not been treated for hepatitis C who have the CC variation of IL28B."

Data from the ADVANCE study showed that patients with the CC variation of IL28B who were new to treatment and received a telaprevir-based combination regimen had the highest viral cure rates compared to those with the CT and TT variations. Data from both ADVANCE and REALIZE showed a nearly three-fold improvement in viral cure rates among patients with the CT and TT variations of IL28B who received telaprevir-based combination therapy compared to those who received pegylated interferon and ribavirin. These differences were observed among patients who were new to treatment as well as those whose prior treatment for hepatitis C was unsuccessful.

Retrospective Analysis from ADVANCE

The Phase 3 ADVANCE study evaluated people who were new to treatment for hepatitis C. The retrospective analysis of IL28B status presented today includes people tested for IL28B genotype (454/1088; 42 percent). Of the patients in ADVANCE who were tested for their IL28B genotype, the distribution of the variations was consistent with previously published studies in people new to treatment. Data from the subanalysis of IL28B status in the control and telaprevir treatment arms (12 weeks) of the study are shown in the table.


Note: The table would not copy and paste but the SVR rate for CT was 71% and for TT was 73%. Si that is really quite good.


http://www.hivandhepatitis.com/2011_conference/easl2011/docs/0404_2010_a.html

.

[pooh55811]

Sorry, here is the link for that quote above:

http://www.hepatitiscnewdrugresearch.com/hepatitis-c-testlikelihood-of-achieving-svr.html

[pooh55811]

You said you are Genotype 1 (do you know if you are 1a or 1b).

In addition, the test result, IL28B Polymorphism CT, means you have the CT genotype which is explained below.

Genetic testing for hepatitis C patients; IL28B Genotypes

About IL28B
IL28B is a gene related to the interferon system. A genetic
region near the IL28B gene is referred to as an IL28B genotype.
There are three variations of IL28B genotypes: CC, CT or TT. These
variations have been associated with a person's response to
treatment for hepatitis C with pegylated-interferon and ribavirin.
Studies have shown that people with the CC variation respond better
to treatment with pegylated-interferon and ribavirin than those
with the CT or TT variations. The CC variation is more frequent in
Caucasians compared to African Americans (39 percent versus 16
percent), which may partially explain the lower response to
treatment observed among African Americans in most clinical trials
of pegylated-interferon and ribavirin.


Do not get alarmed by this result. I am going to copy and paste another article and also any other info I can find. People who have the CT gene do clear the virus. It is just that people with CC clear it easier. But do not let this get you down. Just move forward.

Many of us do not even know if we are CC, CT, or TT, but we treated anyway. In fact, I don't even know if I am 1a or 1b. 1b is easier to treat than 1a. We just have to move forward and treat. We cannot let the various Genotypes and subtypes get us down.