ITMN-191

[Upbeat]

Intermune

BMO Capital Markets analyst Thomas Shrader said results so far show ITMN-191 could lead to better convenience compared with potential competitor VX-95, being developed by Vertex Pharmaceuticals Inc


The company is being seen more as a long-term growth opportunity, especially after teaming up with Roche Group Ltd. in October to bring its hepatitis C drugs to the market. Intermune licensed the rights to ITMN-191 to Roche for a $60 million upfront payment and up to $470 million in future milestone payments.
                                                     Ron

[mikesimon]

Thanks and I'll let you know what I learn. Mike

[jmjm530]

In post C8, HR appeared to be referring to post SVR persistence even though he used the word "occult" -- perhaps in the less precise sense as some do.

And while directly referring to lymphoproliferative disorders and/or mixed cryoglobulinemia, I took it in a very general sense to pertain to any significant post SVR symptomology like perhaps your  enzyme elevations -- with the general thrust being that short-course treatments of SVR may be useful, now with peg and riba and later perhaps with less toxic, newer drugs.

This is what made me think of you and your transplant surgeons current approach. In any event, it seemed to clarify in a very positive way what your transplant surgeon was up to , because when I first heard what he was doing I drew a blank. But maybe I'm just reading this wrong.  In any event, good luck with your meeting. It does seem to me that your doctors are a bit ahead of the HCV treatment curve as you have inferred all long.

Be well,

-- Jim

[mikesimon]

I'm not certain that his remarks pertains to my situation though the end result - treatment - might. I am not showing any symptoms of lymphoproliferative disorders and/or mixed cryoglobulinemia. The info on occult doesn't seem to fit. My situation looks like residual or persistent hepatitis. My best guess is that the TX is designed to halt the liver injury which resulted from my immune response. I will see my doctor soon and we will have one hell of a conversation I can assure you of that. Then I will post what I learn...or what he learns - I'm kidding here. Thanks for keeping an eye out for me. Mike

[Eisbein]

I am passing out. You miss one day of reading, and you are in big trouble.
Like to talk to you, hopefully tommorrow. If this thread goes under, come to the on 11/09 one, or if you prefer another one.

Ina

[jmjm530]

Interesting response by Hepatitisresearcher in his response of 11/15.
http://www.medhelp.org/forums/Hepatitis/messages/43754.html

Seems very much in line with how your transplant physician is handling your case -- specifically with another round of peg and riba, perhaps for just a limited time until things get back under control.

Be well,

-- Jim

[jmjm530]

I prefer my gladiator battles to be in the movies. Spartacus was good, I prefered "Gladiator" with Russell Crowe. Let's try and keep things calm if I may suggest. And yes, no one else got involved thankfully and probably because the multi-thread format buries any particular thread within two days -- that has good and bad points. LOL. But of course your loyal friend found it, as she always does, so it's always me against the pair. LOL. Anyway I think that finishes that and if you want to catch HR from now on, either catch him in another thread or open a new thread up like many are doing.

Just got back from hep doc today and ALT is 16, not that I expected anything else. Actually I'm having drinks with him later this week and I kind you not but wouldn't post that up top unless I was in a particularly frisky mood. Skin is doing pretty well but some very minor erruptions from time to time and that's when I get out the Metrogel or Rezamid. Haven't been using the Clindamycin all that much. Still looking into IPL or PDL laser -- any movement on your part there? So told doc about my "bloating" and he blamed it on weight gain. I'm sure he's wrong but we'll see after I lose around seven pounds which I was planning on anyway. Got the flu shot today after hemming and hawing but he says everyone who worked there just got one so I figured why not.
Also got an rx to re-test hep b and a antibodies again. Per my last possible bad reaction to the hep b vaccine, he suggested a "baby" dose this time to monitor ALT's with a double-dose to follow if I handled it well. Something to think about. Other than that feeling pretty strong and more "normal" than every before.Hgb is actually higher than pre-tx.  By the way, HR's commentary on "trash virus" per the occult/persistent virus thread is in line with what my doc has told me. He's not worried about it nor am I. So how are things going on your end, skin and all? And next time, I get "under your skin" do me a favor and take ten deep breaths, a cold shower or a "hot" moment with your significant other -- whatever works -- and then if you still feel the need post down here. WAY to much drama up there these days for me. Thanks in advance.

-- Jim

[Eisbein]

good grief Jim, I am talking to Mike on another thread 11/09
can I get rabies vaccine by anxious guy.
I am sitting there waiting for your thread to appear, starting to curse at med help.

Meee giving motherly advice to you...excuse,hrhrhr....sorry, had to clear my throat.
You sure do get under my skin, not always in a bad way though.
Did you ever see the movie Spartacus? That's how I envision us...in a ring...I hold the pitch fork in the metal enclaved arm, you got the metal chain...in the end I won't kill you.
I won't, because I recognize that your intentions are good, you are helpful and informed, and like all of us are not perfect.

It turned out as I had hoped...I said to you what I wanted to say, and thankfully nobody jumped to either one of our defense.
I am grateful for Ivette clarifying though, because she said exactly what I meant to say...just so damn difficult for me to put into words.

I got lots to say to you...but you win on paper every time. I would look like a fool next to your posts.
Ain't private down here, are you kidding.

I would give you my phone number though if I knew how... a fireball would be coming your way, I guess you know that already, and I am confided I would hold my own.

Keep that beard soft, girls don't like scratchy vegetable brushes on their delicate skins.

Come up to the other thread, this one will be retired soon.

Ina

[jmjm530]

Ina: Hope this could stay just between us, as we have gone over issues in the past.
------------------------------------
LOL. I got a big chuckle out of that. "just stay between us" and maybe like 500 people reading that thread :)

Seriously, let me make a suggestion. If you really want to tell me something more or less private, just say something like "I posted to you below" and I'll go look for it.  But please, you know my very low tolerance for MH soap operas (and motherly advice :) ) so hopefully it will be about skin issues or  something which I hope are getting better with both of us. Hey, I even can grow a beard now for 3-4 days without a rash. That's even better than pre-tx, however the cold, dry weather is just starting.

Hi Mike, see you hanging down here as well so I thought I'd say hi :)

[mikesimon]

I didn't think he'd have anything meaningful to say but I could be wrong. I have corresponded with eminent hepatologists and no one seems to know anything more than the man I see now and I suspect that they know a good deal less. Mike

[Eisbein]

Trying to keep this thread alive.
I wish hepresearcher would have gotten a glimpse of your situation.
That was a perfect thread for you to chime in, but you have your reasons.

Ina

[Eisbein]

Oki doki.

Ina

[Eisbein]

Hi Mike,
I have no idea if willing reads the board on a daily basis, or if he will check this post again.
Since he comes by so rarely, I am afraid your message may not be seen by him.
When you hear from your doc, you can post his answer here, and if necessary, I can ask him to stop by.
I am sure this subject is of great interest to him.
I can check here every day or so till the thread expiers, but hopefully you will hear from your doctor in the next 10 days.
With these many threads (I hate it), I keep skipping a lot, and I really don't want to miss anything of such importance.
Let me know if this is OK with you, don't want to do anything without your permission.

Ina

[Eisbein]

I can't stand looking at my mistakes, this one really hurts the eyes...expires...good grief.
Anyway, there is plenty room at this post...not so bad having wasted one with grammar correction.

Ina

[mikesimon]

I got a response to my email but it was unresponsive to my question. It wasn't from my surgeon so I may wait until I see him and that might not be until next week or possibly the week after. I'll post here if this thread is still alive or some place where you'll see it. Mike

[mikesimon]

I sent an email asking where/how the HCV RNA was detected and when I hear I'll post. I still don't see how it will explain anything as far as a realistic goal or likely outcome is concerned or how it would affect my treatment decision but if willing thinks it's pretinent I assume that it is. Mike

[Eisbein]

Willing,
now why didn't I think of all of that...LOL

So willing, are you making your living dissecting the housing preferences of the virus, or is this just a little hobby of yours?
Na, you don't have to answer this, just being nosy.

Thanks to you and Mike for the well wishes.
I survived...obviously...and nothing of concern was seen. Biopsies are pending...am I glad this is over.

And Mike, I like to know too, was the RNA from serum obtained by liver biopsy, or from liver cells.
Watch out willing, I am learning, even with the fog.
Now you have Tnhepguy's e-mail, and I am afraid you will have your discussions in private, and forget us little fish...hope I am wrong.

Ina

[mikesimon]

You're right - this is a long way down. My opinion is that MH has  digressed significantly in part because of all the threads. But regardless, thanks again. If it isn't the HCV I have no idea what would have caused the elevation. I doubt it was rejection. As I have told, you my surgeon thought it was HCV just from looking at my labs so apparently it is a situation he's seen before. I'll see him soon and post the results. Mike

[willing]

as best I know, that's the magic of SVR : regardless of the presence of lurking residual virus your immune response is now effective enough to suppress nearly all viral production. Here's yet another study, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16441471&query_hl=5&itool=pubmed_DocSum">Formann'06</a> that underscores the durability of SVR. I could be completely wrong here, but I still have a strong hunch that your ALT spike was due to other causes. Anyway, thanks for sharing all this and please post whatever you learn from your Dr. All the best.

PS : Another possibly related clue here is that the body's ability to destroy floating virions (the "clearance rate" in the kinetic studies) is getting more attention as an SVR predictor. In abstract 350 from this week's <a href="http://tinyurl.com/yms5nh">AASLD</a> Berg and group report on fine-tuning their low VL crierion from 800,000 to 400,000 (retrospectively, it doesn't sound as if they gathered new data) and obtained a very sharp relapse predictor ("statistically highly significant") with the new lower threshold. If the point of tx is not to eradicate the virus but to retrain a defective immune response, those who already have a high clearance rate don't have as far to go...

[mikesimon]

I really appreciate your insight willing and you have given me some new directions to channel my thinking. I will find out soon how the virus was detected and let you know what I learn. I still don't understand why, irrespective of how/where the HCV was detected, it was at such a low VL. Do you have any thoughts on that? Is it merely the "shooting fish in the barrel" scenario that could explain the low level? Anyway willing, I want to thank you so much for sharing your ideas with me. Take care and stay well. Mike

[willing]

boy, takes some scrolling to get down here!

Ina - best wishes for a speedy recovery from tomorrow's assault. The only good thing about it is not having to go through it again for a (hopefully long) while. And sorry if I seem obsessed, from where I'm looking 30IU seems damn nice!

Mike - I think it's actually pretty important whether the RNA was detected in serum/plasma or in cells. After the virus uses the cell to replicate it releases the copies into the extra-cellular fluid (without damaging the cell). The conventional VL tests sample the concentration of "free" virions floating in plasma; only by doing a biopsy and lysing the cells can you actually measure the vial RNA internal to the cells.

Different branches of the immune response destroy free-floating virus and infected cells and the former is like shooting fish in a barrel compared to the latter (hence the dramatic drop in the first 24/48 hours after ifn kicks in, eg zeuzem's slide 28 from the CME link above). Put another way, if the RNA was detected from serum obtained with the biopsy then drawing blood for your next heptimax  nearer to the portal vein rather than from your arm should increase the likelihood of a detectable result. On the other hand if the RNA was obtained from liver cells drawn in the bx, then it measured something no heptimax will ever be able to.

[mikesimon]

I will be thinking about you and hoping that the scopes are absolutely unremarkable. It seems like there is always something to get worried about but yet we do endure, don't we? Good luck Ina. Mike

[Eisbein]

I know Mike, it didn't appear suddenly, I just wrote flippingly.
I do follow your story step by step.
The fact is, you were Heptimax neg for several years, and at a biopsy 30/IU pos. Whether it replicates very slowly, or not at all, whether it is the same old virus you started out with or not, whether or not it was brought on by dose reduction of anti-rejection drugs or not...some part of the virus survived all your treatments, and you are here to tell us about it.
I firmly believe that you are not an isolated case.
And apparently in those that have occult virus, very mild liver damage continous.
So if somebody is around 40 years of age, started tx with beginning cirrhosis, becomes SVR, and has occult virus that slowly continous damaging his or her liver...I guess that would be reason for concern. By the time that person reaches 60 or so, he/she may face cirrhosis all over again. This presumes that that person reverted back a stage or two and had 20 some years to spare.
Yeah, occult concerns me alright, and for many more reasons.
Do I freak out over this, nope, just another concern on the list of many.
I know you tx for 3 years, but time elapsed between treatments.
That makes a difference when I talk about out-treating the life of the virus (which we don't really know how long), which really means tx longer than the life expectancy of a liver cell, which is more important at stage 3 or 4. But maybe that is old thinking now, because it looks like RVR is the way to determine tx lengh.

So you think your high ALT's meant anti-rejection, and your doc thinks it's an overly aggressive immune response.
I would have gone along with your theory.

Mike, if you write here, I won't be able to respond for a few days. I have a endosopy/colonoscopy coming up on tuesday. Got to be in the hospital at 6 AM, and slowly getting ready for what I consider a most disgusting prep.

I know squat about nothing occult virus, just rambling.

Be well, and you are right, I also consider myself lucky to be alive, inspite of all the sh!t hitting the fan with all this post tx stuff.

Ina

[mikesimon]

The 30 IU/ml didn't just appear suddenly - except is the sense that it was only discovered on biopsy June 2006. As I have said, I have not been serum detectable per Heptimax since 2003 and I stopped TX in 2004. I have Heptimax tests monthly so it's not been in my serum at 5 or greater IU/ml. I would not characterize my situation as a relapse. The HCV was almost certainly there all along. The curious thing for me is that the virus replicates at 10 to the twelfth power and yet I only had 30 IU/ml in my liver which, as we know, is the primary site of replication. It must either be that the persistent/occult virus doesn't replicate as prodigiously as the "regular HCV" or my immune system somehow kept it in check... or I guess it could be a combination of the two. I can't say I feel any HCV effects but then perhaps I have had this disease so long that I can't recognize a change or possibly being a transplant recipient makes me less sensitive to changes - I'm so happy and grateful to be alive that I disregard any effects that another might be bothered more by. If I had psoriasis or bone or joint pain that would be impossible to ignore but a little brain fog or the like I might not recognize as abnormal. As to treating long enough that every liver cell would have died: I treated 1 year then another year and then 73 weeks. The first 2 treatments were at reduced ribavirin dose but the 3rd TX was at full dose for 73 weeks straight with absolute compliance so I too treated longer than the normal lifespan of liver cells. Apparently, that's not the solution - for me anyway. Mike

[Eisbein]

My dear mike...you are one of the culprits why I am not in the woods yet:), and lets not forget Willing, Tnhepguy, and DD.
I mean it's one think to read articles about occult stuff, but it's another thing to have a real life person on this forum, talking about 30/IU reappearing suddenly, 2 brains taking occult studies apart, and DD feeding us a steady diet of his concerns.

I had read only about one person relapsing after 8 years, and that was a women who had gammaglobulin something, and than she became neg on her own again.

As long as I am having so many post tx issues, it won't be possible for me to leave hepc alone. When those are gone...wishful thinking maybe...I will have to review my withdrawl options again.

But what am I talking guys, this women here caught every last virus LOL...how the hell can anything be left alive in the liver. I treated twice as long than the life expectancy of a liver cell, and when it goes, the virus goes with it, right.
Pleeease Willing, be nice, forget about all the other places it can lurk, it's gone....hahaha???

Ina