Hep C Discussion Forum

Ro · Senior Member

Understanding the importance Resistant Variant (Q80K)

Ro · Senior Member

Thank you all for your responses and information.. It is so much to take in....

I was told by nurse practioner at my doctor's that I have Stage 2 cirrhosis, 3D scan reports read: "there is a mild prominence of the portal vein suggesting mild aneurysmal dilatation adjacent to its bifurcation" but I was also told that it is compensated.. so I guess that means I have compensated cirrhosis

Doctor is still pushing for the solvaldi/olysio ... where can I find documented data that says to avoid olysio. I am thinking it sounds more promising to wait for S/L treatment to come out. Something I truly want to discuss with doctor, but want to be prepared with facts.

I do have slight esophogeal varicies and was placed on cardivilol twice a day about a month ago....

Again, thank you for all your shared info.

Isiscat2011 · Guru

Tig56 wrote:
I was just trying to help explain it.

It was very thoughtful. You are a good guy, Tig. smile

Tig · Admin

Okay, I'll refrain from posting this type of information in the future. I was just trying to help explain it. The question persists and when people search for it, these are just a few of the examples they are finding. Thanks for pointing this out. I appreciate it.

Tig

patiently_waiting · Senior Member

I always thought it was considered "fibrosis" till you got to stage 4 and then it was considered cirrhosis, but apparently I had my wires crossed. I think I get it now. Thanks for explaining.

mallani · Guru

Hi Tig,

Sorry to be picky, but I would like to comment on your references.

Livestrong and Buzzle links are obviously written by lay-people who do not understand what cirrhosis is.

About Hepatitis explains the Metavir score for Fibrosis/Inflammation.

Depts. Washington is supposedly published in 2006. It states cirrhosis is diagnosed by 'bridging fibrosis' which is incorrect. This is used for F3's. Also 'irreversible scarring' is now been shown to be incorrect. The Stages mentioned went out in the 1990's. It was recognised that many well-compensated cirrhotics could develop varices that bled. The degree of portal hypertension required to develop oesophageal and/or gastric varices, varies considerably from person to person. Also small varices can bleed, due to a variety of causes, including reflux and diet. Decompensated cirrhosis implies ascites due to portal hypertension/ decreased albumin, encephalopathy, hyperbilirubinaemia (jaundice) and recurrent bleeding from varices or portal hypertensive gastropathy. The change from compensated to decompensated is slow, with possibly only one feature appearing, but I am assured there is no longer any 'Staging'.

I guess it doesn't really matter. All cirrhotics need treatment if they can cope with it. Cheers.

Tig · Admin

There seems to be frequent references made to stages of cirrhosis. I don't understand why there isn't a more definitive explanation made available to the public by the medical community on the subject. We know (as mentioned) that cirrhosis is either "compensated" or "uncompensated". But there are also references online that do describe cirrhosis in stages and I'll provide links to some examples. I hope it will help explain why some doctors are using this to describe the individual's cirrhotic progression. It's confusing to hear all of the different terms and methods used to describe medical conditions in general. Hopefully this can help explain the differences. As PW mentions, fibrosis and inflammatory scores are listed in stages or levels, which might add to the confusion as well.

Tig

http://www.livestrong.com/article/240024-what-are-the-4-stages-of-cirrhosis/

http://www.buzzle.com/articles/cirrhosis-of-the-liver-stage4.html

http://www.natap.org/2002/Oct/103002_2.htm

http://hepatitis.about.com/od/diagnosis/a/Metavir.htm

http://depts.washington.edu/hepstudy/definitions/?let=c : (below)

Compensated versus decompensated cirrhosis: Patients with cirrhosis can be categorized as having compensated or decompensated cirrhosis. From a clinical standpoint, patients with compensated cirrhosis have no clinical manifestations of portal hypertension. Some experts divide compensated cirrhosis into two categories: stage 1 (absence of varices) and stage 2 (presence of varicies without bleeding and abscence of acites). Decompensated cirrhosis is characterized by the development of clinically-evident complications of portal hypertension (ascites, esophageal variceal bleeding, or encephalopathy) or liver insufficeincy (manifested by jaundice). Some experts categorize decompensated cirrhosis as stage 3 and stage 4, with satege 4 considered as severe decompensated cirrhosis and characterized by recurrent variceal hemorrhage, refractory ascites, hyponatremia, and/or hepatorenal syndrome. The prognosis and survival with decompensated cirrhosis is dramatically worse than those with compensated cirrhosis.

patiently_waiting · Senior Member

I think she probably meant stage 2 fibrosis and not cirrhosis.

mallani · Guru

Hi Ro,

The Q80K polymorphism is only a problem when Olysio is used as the principal DAA. When combined with Sovaldi, it's presence did not seem to affect results.

You are probably not Interferon-sensitive, so I would avoid that.

I'm not sure what 'Stage 2 cirrhosis' is. Cirrhosis is either compensated or decompensated. In any case, treatment is fairly urgent.

Having failed treatment with an antiprotease ( Incivek) , I would personally try to avoid retreatment with another antiprotease (Olysio). Only your doctor can decide whether you can wait for the magic Sovaldi/Ledipasvir pill. He would assess this with various Lab values, like Albumin, Platelet count, INR (Prothrombin time) and bilirubin. Have you had a recent gastroscopy for varices?

Best of luck.

Isiscat2011 · Guru

Ro wrote:
I am not fully understanding all this. I just got told Q80K NS3 is detected . I have been treated unsuccessfully with peg/riba; infergen/riba; also incevik/peg/riba during the course of the last 10 years. I am now told I am stage 2 cirrhosis ... I had been appealing insurance company to get payment for solvidad and olysio.. but now am VERY confused.. the medical team I go to believe the treatment will be successful.. I am so hesitant and wonder if I should wait for the next approved treatment.. what is the alternative treatment options for patients found to be infected withthis polymorphic variant?

Hi Ro:

Mallani will probably be along soon and he is hands down the most knowledgeable about complex science and medical issues. I'm pretty sure his medical degree has something to do with that. In the meantime, I'll tell you what I have learned, because you and I are in a similar situation. First, there is no such thing as stage 2 cirrhosis. There is compensated and decompensated. I am assuming your liver is still compensating.

My understanding is that the Q80K is only a problem for Olysio but when Olysio is taken in combination with Sovaldi it should not be an issue. This is because Sovaldi is particularly good at cleaning up RAVs. There have been some studies done with the Q80K polymorphism and this is the conclusion that was reached. It is noteworthy, however, that all information pertaining to the new HepC treatments is very new and nothing is set in stone.

Whether to treat now or wait is a very individual decision. You could treat with the S/L combo when it comes out. Your SVR odds would be better with the S/L (according to the clinical trial data your odds are 100% if you treat for 24 weeks). Reportedly, the side effects are moderate with both the S/O and the S/L.

The downside is, of course, that the virus stays in your body longer if you decide to wait. The significance of that is unknown; it depends on how the virus is effecting you and how rapidly your liver is fibrosing (which is determined by genetic and environmental factors).

You should win your appeal given that you have cirrhosis and also treated with Int/Riba before but I don't know how long that will take. I would expect you will win before the S/L combo is on the shelves.

Either way you go it looks like it will be a fight with your insurance company to pay for the Sovaldi, which is something I expect we will be seeing a great deal of, in the near future. Don't despair over that, however. Sovaldi is making plenty of money and they will pick up part of the tab for the tx in many cases. One way or another you will get your tx but you will need to be the one to decide which tx you want.

Ro · Senior Member

I am not fully understanding all this. I just got told Q80K NS3 is detected . I have been treated unsuccessfully with peg/riba; infergen/riba; also incevik/peg/riba during the course of the last 10 years. I am now told I am stage 2 cirrhosis ... I had been appealing insurance company to get payment for solvidad and olysio.. but now am VERY confused.. the medical team I go to believe the treatment will be successful.. I am so hesitant and wonder if I should wait for the next approved treatment.. what is the alternative treatment options for patients found to be infected withthis polymorphic variant?

mallani · Guru

Hi Matt,

The FDA is trying to help Labcorp to sell it's HCV Genotype NS-3/4A assay. It acquired it from Monogram Biosciences for $M107 in 2009, and they started to promote it in late 2011, testing for mutations against Victrelis and Incivek.

The RAV known as Q80K is only important for Olysio. As ~35% of HCV patients have this mutation in their quasispecies, it's another reason why Olysio is a poor drug.

The Victrelis and Incivek RAV's are well known, and whether they are present at the start of Rx doesn't seem to matter. Peg and Riba clean them up. Without Peg., it would appear we need another DAA to mop them up. Sofosbuvir is very mutation-resistant, and MK-5172 also seems to be able to cope with most known RAV's. Here's a list of significant RAV's for some of the DAA's. Cheers.

http://www.idsociety.org/uploadedFiles/IDSA/Hepatitis_C/For_IDSA_Members/ForumforCollaborativeHIV-ClinicallyRelevantHCVDrug.pdf

Matt Chris · Guru

Hey all

In most future HCV DAA's treatments we will have to understand the importance of our base line Resistant Variants before we start a treatment. The following article is a good primer to gain some knowledge about it.

follow this link http://hepatitiscnewdrugs.blogspot.com/2013/12/olysio-simeprevir-what-is-resistant.html

Now before treatment their will be blood tests to determind some of our possible Rav's . I believe Lab Corp. is already setup to do these tests.

Here is a small excerpt from the article

" As mentioned, given the high frequency of the Q80K polymorphism in the U.S. population and its significant negative impact on rates of SVR12, according to the prescribing information, the FDA is recommending that all Genotype 1a patients be screened for the Q80K polymorphism. Alternative treatment options should be considered for patients found to be infected with this polymorphic variant.

matt

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