Genotype 3 news

[Bill1954]

“HCV Genotype 3 May Be Associated with More Rapid Liver Fibrosis Progression in People with Chronic Hepatitis C”

http://www.hivandhepatitis.com/hep_c/news/2009/102709_a.html

This just arrived in my inbox; I thought it was worthy of reading. Of particular interest to genotype 3 patients, Dr Stefan Zeuzem mentions:

“While some people with hepatitis C and their clinicians are awaiting new oral specifically targeted antiviral therapies (STAT-C), Zeuzem noted that the drugs furthest along in the development pipeline -- the HCV protease inhibitors telaprevir and boceprevir -- are most active against HCV genotypes 1-2 and less so against genotypes 3-4, while non-nucleoside HCV polymerase inhibitors are generally primarily active against genotype 1.

"Taken together, [the] combination of peginterferon alfa and ribavirin could remain the key treatment option for patients infected with HCV genotype 3 in the years to come," Zeuzem concluded. "If indeed fibrosis progression in patients infected with HCV genotype 3 is faster than in HCV-1 infected patients, waiting for new treatment options should be strongly discouraged in this patient population."

Bill

[Kristina538]

Wow, that's a turnaround!!   And to think many of us '3's' were last in line for second tx because our progression was slower.  (or maybe that was just a line delivered to me at the time because they thought my progression was slower).

Thanks Bill;  it was interesting to see that the new drugs are definitely pointing towards G1 and 2.  I had thought it was G1 in particular.  It's probably about time the G2 and 3's were divided but now they've got G3 with G4 hehe!!

[copyman]

very interesting bill. it wasn't that  long ago that 3's were grouped along with 2's as being the better GT to have. When I say better I mean easier to treat. you just never know with this disease.

[Bill1954]

I thought this was interesting too. While much of this content has been discussed before in here, it’s good to see it pulled together in one place by a highly regarded researcher.

There’s a GT-4 patient in here that was asking about the efficacy of PI drugs to his genotype, although I can’t recall who it was. This suggests GT-4 might be less responsive to the new treatments too.

Bill

[RCM829]

Thanks Bill. Great information.

As a geno 3, I suspected this when I chose to retreat with standard Pegasys/Ribavirin earlier this year. Being "only" stage 2, some questioned my decision and felt it better to wait. I felt otherwise.

This is where this website excels. This information can potentially help other geno 3's manage their disease - and subsequent treatment options - more intelligently

[FlGuy]

In some respects the information in the summary is good news.  There is so much gray area in a lot HCV information and conflicting slants to much of it. Assuming that the information is valid and not strongly disputed a Geno 3 could process as "PI's are not so effective and fibrosis is faster".  With that kind of message it could be a whole lot easier to s&it AND get off the pot.

[Marcia2202]

Thanks for posting this Bill.

I must have been one of the lucky ones. G3a, infected over 25 years F0-1... treated 8 months--- SVR

[DragonSlayer45]

I am a little puzzled about this article and what Dr. Zeuzem says. He stated

“While some people with hepatitis C and their clinicians are awaiting new oral specifically targeted antiviral therapies (STAT-C), Zeuzem noted that the drugs furthest along in the development pipeline -- the HCV protease inhibitors telaprevir and boceprevir -- are most active against HCV genotypes 1-2 and less so against genotypes 3-4, while non-nucleoside HCV polymerase inhibitors are generally primarily active against genotype 1."

The phase 1 trials of R7128, a polymerase inhibitor, had a success rate of 90% on geno 2 and 3 when used with peg and Riba. That was with geno 2 and 3 non-responders. So i am not sure what he is referring to.

That is what is exciting about that drug that it seems to be effective across the board. The phase II trial I believe is also going to incorporate treatment naive geno 4's as it has shown to be effective with invitro studies with genotypes1 through 4.

[Bali05]

Hi Bill,
That GT-4 patient your are referring to would be me.
So first they want to group me with 1 now with 3 ?
It appears that whenever there is a situation where geno 4 is being
grouped it will be grouped with the less favorite treatment option.
How about some solid geno 4 trial data for a change like Romarks Nitazoxanide trials?
As far as I know in reference to PIs and geno 4 they are just starting to
recruit in US. Other than that there is a trial in Ireland but I have not seen any results.
Interestingly enough trials in countries that are geno 4 dominant do not get
much acceptance in the US. For example there was a trial in Egypt (not by Romark)
that showed  no difference between 36wks and 48wks of SOC other than more
severe sx for 48wks. Another one showed 86% SVR rate for early responders
with 24wks SOC yet no hepatologist seems here  wants to see this. Instead as a geno 4 you will be grouped with geno 1 with standard 48wks no matter what.

I am told that Telepravir was specifically designed for GT-1 but do we have trial data
what it does to 4 ?

Here is what a Chief Hepatologist who is envolved in trials answered me:

Q: If I turn out to be a nonresponder or relapser would Telepravir be a possibility for retreatment of geno 4 in the future  when it becomes available?

A:
Yes - the sustained virologic response rate is in the 40% range for nonresponders and 60-70% range for relapsers

Now I ask myself where are those numbers coming from ? geno 1 trials ?

Looks to me like it is still to early to tell what is going to be the situation in the next two years. The general advice from any hepatologist is to treat as early as possible which of course makes sense .The only problem is nobody addresses the possibility
of failing treatment and loosing naive status for upcoming trials.

Bill, I very much appreciate you keeping me in mind in your post and please continue
to let me know anything you might come across that pretains to GT4.

thanks

Bali05

[Bill1954]

Dragonsalyer—

Thanks for your thoughts. I was previously unaware R7128 had these capabilities with GT-3; and thanks for the info on GT-4. If you have any links that support this data, I’m sure other GT-3 patients will appreciate it. It’s difficult to keep in front of new developments with all the drugs in trial now, so thanks again for your input.



Bali—

It must be frustrating to have an ‘orphan’ genotype; not enough infected in the states to make comprehensive studies economically feasible. I’ll keep my eyes open, and report anything that looks interesting to you ASAP. Good luck—

Bill

[Bali05]

Bill,

Frustration does not even begin to describe it.
One of the first hepatologists I spoke to
said when I made him aware of the March2009 Gastroentereology article about
improved response rate for GT4 and Nitazoxanide that his issue was still wrapped
in plastic and he did not have time to read it (that was in July!).In his opinion I was
looking for a "Superstar" hep C treater and he wished me good luck finding one.
Well I have found several but that still does not mean it is my best next move
in this chess "game".
I took 3 months of string pulling alone to get a script of Alinia , now sitting on my desk.
Since June I learned it is a multi fold process of:
1) finding out what treatment exists or will exist in the near future
2) making it a reality , finding doctors willing to work with you
3) once it is all on the table deciding what you ACTUALLY are going to do based on what you learned up to this point and think long and hard about the consequences.

Thanks for your help.

Bali05

[BelB64]

I too feel this might be overblown with incorrect information. As dragonslayer states R7128 a polymerase inhibitor had results that were equal for Geno 2s and 3s. Nowhere did they say it was MORE effective for 1s.  Pharmassett have stated many times that the beauty of this inhibitor was that it was successful across genotypes and that they already have a new inhibitor that is 20 times more potent than R7128. As far as geno 3 is a more rapid progressor, I believe in the study it states this might not actually be true because the geno 3s in the study were mostly ACTIVE intravenous drug users and this might have skewed the figures. It seems strange that for all these rapid progression was caused by when you were infected (over 35) gender (male) and  alcohol consumption (over 3 or 4 per day)  Geno 1 was also considered to be the "worst" type.

[BelB64]

I'm also glad the article said genotype 3s MIGHT progress faster because as we all know there are many studies that contradict this. One famous one is the study printed on the medscape website

www.medscape.com/viewarticle/554637

Their results here are quite clear: "There was no association between rate of fibrosis progression and genotype" In fact there was one cohort, women who were infected before age 37 who were NON-Genotype one were progressiing at a rate so slow that they were on pace for cirrhosis at age 89!  

I believe the reason some Genotype 3s would progree "faster" is simply that many as I said in an earlier message still use intravenous drugs which promote fibrosis progression and genotype 3s do have steotosis more that the other genotypes and that does on occasion promote progression.

To find out what is really going on, wouldn't a study of who needs transplants or who developes cancer of the liver determine if one genotype or another is more likely to progress rapidly?

[Kristina538]

I'm not 89,  carried my G3 HVC for 26 years, and have (had?) bridging fibrosis.   Any intravenous drug use stayed in the history books of the early 80's.   I seem to be a contradiction to your theory which, I believe, may be on shakey ground.

If you're going to target behaviour, there are many other areas you could also bring into the mix; alcohol, cigarettes, fatty food, lack of fluids, no exercise,  tatoos, sexual behaviours.... and the list goes on.

I agree that steatosis does come with the G3 prognosis, but I would be interested to see a study that supports your general theory that G3's progress faster because they continue using intravenous drugs.  

[DragonSlayer45]

Bill,

I just read this and I am running out he door but here is a quick article from last years AASLD I believe:

http://www.hepctrust.org.uk/news/2008/News+From+AASLD+Liver+Conference+2008/AASLD+2008+-+HCV+Polymerase+Inhibitor+R7128+Demonstrates+Good+Antiviral+Activity+in+Genotype+2+or+3.htm

I couldn't find the article talking about the geno 4 info I read before but here is a link from Roche that mentions the Phase 2 trial and an arm for treating geno 4 naive patients. Gotta run.

[Bill1954]

Thanks everyone, for providing the study info and different views; I can’t answer for Zeuzem; its beginning to appear there are other ways of looking at this. Take care, all—

Bill

[BelB64]

Kristina- These are not MY theories. The first one I mentioned stating cirrhosis wouldn't happen until age 89 for females who contracted the disease before age 39 and were non-geno 1s was a Medscape study. It didn't say ALL would respond the same way, only that on average it would be this way.

As for the fact that intravenous drug use could progress fibrosis faster, thus skewing the data, it's right in the full text of the study Bill1954 quoted. Here is what it said when saying they couldn't for sure say the results were unquestionable

"authors cannot rule out other confounding factors e.g. that patients infected with genotype 3 infection may have had a higher exposure to liver toxic agents beyond alcohol e.g.continued use of illicit drugs.