Calling SonicBandAid...Jim said mebbe to talk to you

Hi Sonic:

Would you mind having a look at my post on the other side regarding my Gish visit today?

I'm an acute RVR overweight but UND at weeks 2 and 11. He told me today that I had to go 48 weeks. I was shocked. There's more info on the other side.

Many thanks in advance,
Deb

[SonicBandaid]

Yeah, thats what they concluded, I just don't reach the same conclusion from their [and the other acute studies] data.  I think 71% is not acceptable if higher rates of clearance is acheived during shorter duration therapy; I think this really means they should have continued treatment for the full 48 weeks.
Cheers,
SB

[Forseegood]

I hope that you get things resolved to something comfortable and effective for you. As an aside, he's too far from me, but I would love to consult with Dr. Gish, he works with and co-authored a book on Hepatitis C with conventional therapies- and Chinese herbs with Misha Cohen (if this is the same Doctor I'm thinking of)...he must be a very open minded Doctor and I've heard so many good things about him...he sure is famous in the hepatitis community...

[Forseegood]

Hi, while I have your attention (if I do) just wondering which one of the new clinical trials peak your interest the most? Sorry if you've answered this question already (haven't been around in awhile) I wouldn't be surprised if you have...course, if you have time, thanks so much!

Debnevada: sorry about the hi-jack, only figure it would be a short exchange...thanks!

[SonicBandaid]

Hi Forseegood,
Like everyone else I am really interested to see the long-er term data on the protease inhibitors (any and all of them), although I am not optimistic (but hope to be proved very wrong).  I think the albuferon trials will show pretty much what we see with PEG-IFN, maybe a few points better, but with reduced side effect profiles (and that will be good).  I think the real interest will be in the small molecule - polypeptide inhibitors of HCV-RNA-polymerase function, some of which may get to clinical trials in the next 12-18 months. Iam looking forward to the next AASLD (Nov 2-6, 2007) and EASL (2008) meetings as these will likely showcase some of this stuff.
Cheers,
Sonic

[Forseegood]

Gee, thanks so much for your quick response! Much obliged! My doc told me at the last conference, guess it was Barcelona? That he spoke to some trial docs re the albufuron, and a few had told him that their patients only SVRed a few points more on average (guess any points are better then none, statistically speaking) but, they did report a better side effect profile, on average...guess it's a question of thanking the heavens for small favors, I'm all for fewer side effects!...

I, maybe too optimistically, get encouraged by a lot of the results I'm seeing with the Vertex trial participants here on this board, but like you said, it's a question of watching for some more data to come in...And now, there are more trials being run out of my hospital, with exotic sounding names of course, that I know nothing about....

Once again, thanks so much for your response...I imagine you go to the Austrailian board as well? Such nice folks...I love the sense of humor and lack of pretention in the culture, how's that for a broad swath of a general statement?:) anyway, be well...

[jmjm530]

Yes, I believe Deb is geno 1 (not 100% sure) but the reason for the surprise is that Deb said she was diagnosed as acute and treated within the acute window. My understanding is that acute cases are often treated with different protocols (including shorter periods) with excellent results. Add that Deb being non-detectible at week 2, mix in what appears to be some significant side effects from the treatment drugs, and you would think she would treat less than 48 weeks.

I understand you might not want to comment directly on a case handled by another doctor (one you appear to know or at least know about)  but maybe you could at least comment in general on acute treatment protocols.

My guess is that perhaps her doctor might have doubts about whether she was actually acute and/or have concerns about her weight -- perhaps he believes she has fatty liver.
http://www.medhelp.org/forums/Hepatitis-Community/messages/1203.html

My suggestion was first to ask her doctor the reasons why he wants to treat 48 weeks. Depending on what he says, Deb then might pursue a second opinion, regardless of the excelllent reputation of Dr. G. -- if for nothing other than peace of mind. My liver specialist also had an excellent reputation, but I ended up consulting with additional hepatologists regarding some critical treatment decisions -- because as you know, even the "top dogs" don't always agree on the best way to chew a bone (or even whether to chew it), and in the end it's your liver that's being treated, not theirs.

-- Jim

[debnevada]

I'm a geno 4.
He agrees that it is likely that I am an acute
(I was a regular blood donator with last donation june 2004)

deb

[SonicBandaid]

Sorry Jim (If I may be so bold as to use your first name);
I misunderstood the "acute RVR" to mean debnevada had acheived an RVR "acutely" rather than what I should have assumed which was debnevada had acute HCV and and achieved RVR.

This is tough.  While I think it is highly probable that debvevada will clear (probably >70%) after the therapy she has had, the longer term data on treatment of acute HCV is troubling to me, and I think I would encourage patients with type 1 to persist for 48 weeks, and I am sure BG is intending; The original acute HCV  by Jaekel was extremely promising with about 98% of those treated experiencing short term viral clearance (not SVR by definition) (94% in the Sanantonio study).  The more recent study (that followed up and extended the original study by Jaekel), reported by Wiegand, suggests an SVR rate of ~71%, that I take to mean the longer you follow people treated acutely for 24 weeks the higher the relapse rate. In this light, if I were devnevada, I would continue therapy until 48 weeks; we all know that your first attempt at interferon is likely to be your best, and given the results devnevada has "enjoyed" (I don't know anyone who has enjoyed IFN) thus far it would be a pity to allow premature cessation of therapy, encouraged perhaps by the early acute results, to jeopardize her chances on long term sustained SVR.  I am certain BG is thinking along these lines.
Hope this helps

References

1. Jaeckel E, Cornberg M, Wedemeyer H, Santantonio T, Mayer J, Zankel M, Pastore G, Dietrich M, Trautwein C, Manns MP: Treatment of acute hepatitis C with interferon alfa-2b. N Engl J Med 2001, 345:1452-1457.
2. Santantonio T, Fasano M, Sinisi E, Guastadisegni A, Casalino C, Mazzola M, Francavilla R, Pastore G: Efficacy of a 24-week course of PEG-interferon alpha-2b monotherapy in patients with acute hepatitis C after failure of spontaneous clearance. J Hepatol 2005, 42:329-333.
3. Wiegand J, Buggisch P, Boecher W, Zeuzem S, Gelbmann CM, Berg T, Kauffmann W, Kallinowski B, Cornberg M, Jaeckel E, et al: Early monotherapy with pegylated interferon alpha-2b for acute hepatitis C infection: the HEP-NET acute-HCV-II study. Hepatology 2006, 43:250-256.

[SonicBandaid]

Hi debnevada,
Genotype 4 probably should be regarded in the same way as genotype 1 as it is much harder to treat than genotype 2 or 3, as you know, hence my agreement with BG's approach is unchanged.  
Cheers, and good luck with your therapy, debnevada
Sonic

[jmjm530]

Sonic: The more recent study (that followed up and extended the original study by Jaekel), reported by Wiegand, suggests an SVR rate of ~71%, that I take to mean the longer you follow people treated acutely for 24 weeks the higher the relapse rate. I
--------------------
Unless I have the wrong article or reading this incorrectly, Wiegand in a recent paper here concludes that the optimal treatment duration for acutes is 24 weeks using a combination of Peg and Inf. Did the cohort you mentioned (around 70% SVR) treat with SOC or with interferon alone? Deb, I believe, is on SOC.

"...Considering these data, we suggest treating acute HCV infection for 24 wk, starting immediately or at three months after onset of the disease, using a combination of PEG-INF and ribavirin in a dosage recommended for treatment of chronic HCV infection (see below)..."
Full article here: http://www.wjgnet.com/1007-9327/13/1897.asp

[debnevada]

i guess i have to agree.

The other factors are what is troubling me...the stuff i have to do and deal with at the same time i have to treat for that long.

deb

[andiamo]

You said that you are not optimistic about the protease inhibitors.  What is the reason for that and why do you think the polymerase inhibitors will be more effective?  Is this based on experience with thew AIDS drugs?
Thanks

[SonicBandaid]

Hi debnevada,
Bob Gish is an excellent hepatologist (as is Mike Fried, also mentioned in this site).
My guess is that you are genotype 1 (I didn't see this in your posts), in which case 48 weeks is standard (and optimal) advice; While your RVR STRONGLY suggests you will clear virus, and this it is POSSIBLE this might occur with 24 weeks therapy, your best bet (assuming you are genotype 1a/b) is to go for 48 weeks therapy.  Pain in the butt, but Bob is trying to be sure you don't relapse.
Cheers,
Sonic

[debnevada]

By the way, MANY thanks Sonic and Jim for that lively interchange.

I know what I have to do.

Deb

[SonicBandaid]

Dear andiamo,
Yes.  I hope I am dead wrong, but the nature of riboviruses (RNA based viruses) is an enourmous ability to generate mutations, and I suspect resistance to these drugs will develop rapidly. We see that with HBV already.  Again, I hope I am wrong.
Cheers
SB

[SonicBandaid]

Sorry, I don't know the answer to how long the new drugs will take to come out.  Obviously there is enormous pressure on companies to get these agents into trials, but this is an enormously expensive process.  Also, given the nature of these drugs toxicity is a major potential concern, so careful preclinical testing is essential.  My guess is that 3-5 years is about right.

Yes.  Hameophiliacs are especially difficult as they are often infected with multiple genotypes. After 3 treatment (I assume IFN, IFN-Riba and Peg-IFN-RIBA) failures, I'd suggest waiting until better combination therapy is released.
Sorry I can't be more positive,
Cheers,
SB

[jmjm530]

With respect to you and Dr. G, I'm still not convinced. The 71% figure you cite seemingly comes from this earlier study by Weigand which reads in part:

"...End-of-treatment response and sustained virological response were defined as undetectable HCV RNA at the end of therapy and after 24 weeks of follow-up, respectively. In the total study population, virological response was 82% at the end of treatment and 71% at the end of follow-up. Of 89 individuals, 65 (73%) were adherent to therapy, receiving 80% of the interferon dosage within 80% of the scheduled treatment duration..." Abstract here: http://tinyurl.com/3x7fxp

Also of note is that this study uses only Peg (no riba) per Weigand's latest recommendation (see previous post) where he recommends 24 weeks of Peg and riba as the optimum tx for acutes. Also, if you take the sub group of compliant patients -- 80/80 rule -- then you get an SVR rate of 89% ON PEG ALONE. I believe Deb has been 80/80 compliant (80% of the meds, 80% of the time) but not sure.

Deb, I know you mostly deal with the NP, but you might want to copy the studies cited and ask Gish what he's basing the 48 weeks on. At least I would do so, but then again, I'm often not the most popular patient in the waiting room :)

-- Jim

[jmjm530]

I clipped that quote in the last post. It should have read:

"...n the total study population, virological response was 82% at the end of treatment and 71% at the end of follow-up. Of 89 individuals, 65 (73%) were adherent to therapy, receiving 80% of the interferon dosage within 80% of the scheduled treatment duration. End-of-treatment and sustained virological response rates in this subpopulation were 94% and 89%, respectively..."

[debnevada]

I missed two doses in the last 11 weeks and that was due to that illness i had...other than that totally compliant. I'm even caught upon on the IFN.

[jmjm530]

Did you skip two injections in a row? If so, that might factor into the decision, even if you did 80% of the meds, 80% of the time. But still, the fact you are non-detectible is certainly a good sign.

-- Jim

[nygirl7]

If 48 leads to higher rates of clearance and less chance of relapse - why would anyone want to attempt the 24 weeks unless their sides were simply devastating?

We all know the first round of IFN is the best round - I can't imagine not shooting for the higher odds and never having to do it again.

But then again I am a 72 weeker and that just shows I am biased.

[debnevada]

Nope. I missed two doses of riba through vomiting while i was ill. I was two days late with my tenth IFN due to fever and on time for the eleventh. And will take 12th tomorrow.

Deb

[SonicBandaid]

Sure, with regard to:
"With respect to you and Dr. G, I'm still not convinced. The 71% figure you cite seemingly comes from this earlier study by Weigand which reads in part"

I understand all that and what Weigand et al concluded.  I just don't agree.  My philosophy has always been if you are to treat HCV (or any disease for that matter) the best approach is to use the most effective drugs first off, aas you may not get a second chance.  I have never seen the logis in NOT using Riba even for acute cases, and always will give it as well.

Sure the side effects are a pain, and prolonging the therapy a REAL pain, but compared to having to repeat the therapy for another year if you fail first time?
I know what I would do myself, so thats what I suggest to patients,
I'll be away for the next month or so; going scubadiving, Be well all
cheers,
SB