HR - Question about retreatment

[returntosender]

HR, if you have finished digesting your Thanksgiving turkey, I have something to ask you.  I am a male, 56, 300lbs, 6'4 Geno 1a, Biopsy, is 2-3 - completed treatment on June 1, 06 after 48 weeks of Peg 180 and Riba 1200.  Cleared at 4 weeks, and stayed clear througout tx including clear on Heptimax on Sept 1.  PCR on 11/17/06 indicated a HCV RNA of 66,200.  All other blood levels within normal limits.  During tx had some reduction of Hgb but not treated for anemia.  No rescue drugs at all.  Most blood tests were OK during tx.  Doc says to lose weight, down to 200 or so and retreat for 72 weeks using same protocol.

My first question, is it possible that this result is in error? Am I wrong to want this confirmed by another test?  My doc thinks so.  Is it possible that this is a spike that the immune system could handle? In other words, is it possible that these small spikes occur but are handled by the immune system or is this amount (66000) an indication that the battle is lost?  Have you ever seen a viral load at the end of tx that goes back to undet without tx?

As to retx, losing weight is going to take a while for sure.  My thought is that I would like to go back after this thing while its down.  I dont like the idea of letting virus do more damage and making me harder to treat. Seems like it would offset the weight loss. Upping the Riba is not popular because of toxicity.  What about using same amount for longer period of time but start it now?  Is that a resonable way to approach this?  Any thoughts, ideas would be most welcome.

[copyman]

sorry that your test showed the dragon returned and i hope it was a mistake. i can not believe your doc would tell you to lose 100 lbs, that is absurd. how does he think someone could do that, to do it safely would take a few years. and besides you are 6'4 so even 50 lbs would be good. what about re-treating with higher dose rx, perhaps at least the riba to 1600 or more? ask your doc about that or find one that  will entertain that idea. you need an aggressive doc to treat the hep c not weight watchers. just my opinion. best of luck to you.

[FlGuy]

When you reconside tx, you should talk to the doc about riba dose. At your weight, and whether you consider riba dose at 13 or 15 mg per kg you'll probably be looking at 1800 or 2000 perday (that's at 136 kg).  For my tx part 2 - doc upped the riba by 50% (in week 5 now).  But, if you do it again - something's gotta change.  It makes no sense to do the same tx again.  Could be the ifn too.  You were taking the same amount as someone half your weight.

[returntosender]

Is there anyone out there actually taking 1800 or 2000 mgs of Riba a day?  Is that considered "off label"?  Is weight based Riba something that docs are doing?  FL, for your retreatment you said you upped the Riba, how much are you taking?  How long did you treat first time and how long did you wait for retx?  Copy, I definitely agree with your statment about weightwatchers, I feel like my doc lost interest as soon as the virus returned.  I dont feel she was very active during tx at all. She is a gastro who specializes in liver cases but I dont think she is on a par with some of the local hepatologists.  Also, I dont get the distinction really about the specialty of hepatology.  Some docs are board certified hepatologists, other are board certified gastros specializing in hepatology, some have studied under certain hepatologists - who am I looking for that will be on cutting edge and will not be afraid to get in there and get rid of this thing?  I have had enough of this "excuse me" style of care, I want someone who will commit to treat this disease. So far I have either found guys with great credentials who were assho!es or not so hot on the creds but who were caring and called me back.  Is it possible to find someone who knows what they are doing AND gives a sh!t?

[DoubleDose]

As you already know, I concur with what was said above.  The Riba seems to be the key variable in question, and since you were already undetected for the great part of your tx, and for at least three months post tx, then the inf. seemed to be doing its job.  You could benefit by also switching to Peg-Intron, but that does not really seem necessary in your case.  Also, I agree with the others that your Riba needs to be in the 13 mg. /kg to 15 mg. /kg range, and I would think that would mean at least 1,600 mg/day or more.  Losing a little weight while preparing for tx, and during tx also will probably be of help, but should not be the 'pre-condition' for your next tx.  I also think that the 72 week protocol is almost MANDATORY in this case, since you relapsed, for whatever reasons.  We can't just assume the extra Riba will be the only thing that needs to be changed, since length of tx also seems to be an improtant factor as well, in cases of GT-1 relapse.  I know you were an RVR, but even so, with a relapse, you will need to err on the 'safer' side, rather than make any assumptions.  

I am convinced that the SVR is there for the taking, but the Riba issues, and length of tx issues will need to be dealt with.
Your doc could monitor your Hemo numbers if you use much higher riba doses, and be ready to intervene with Procrit when necessary.  This is a case where I think you almost will want to provoke a steep red blood cell drop, just to make sure you are doing enough Ribavirin.  

I am also curious to see what HR's take is on your unusual relapse situation.  Your next PCR will also answer some of your questions...I hope one is in the works now.

Good luck to you, and keep the 'game face' on until you beat this virus.  You WILL succeed, and I'm betting on it!

DoubleDose

[returntosender]

Thanks DD, nice to know you are out there - its comforting.  It will be nice to hear what HR has to say about it.  I think you said before that you treated and then relapsed and treated again. Did you go right back at it?  How long did you tx the first time?  What did you do differently the second?  I recall that you really were aggressive or you wouldnt have your nickname I guess.  What exactly did you double dose, the Peg or the Riba or the entire treatment? LOL

[DoubleDose]

I retreated about 18 months after my first relapse.  My first tx was a tough one, and it took me almost eight months to get undetected, which was a bad sign in itself.  I started with 3x/wk intron, and 1200 Riba,(the old standard) and ended up going quickly to daily intron with the 1200 Riba.  Finally after seven months and a lingering low viral load I switched to Infergen, and did 15 mcg./two times daily!!!!  for two weeks, and got undetected immediately, then dropped back to "Only" once a day Infergen at 15 mcg. /day, along with 1,200 Riba.  My red cell count had been dropping drastically, so I had to cut the Riba to 800 mg/day then 600 mg./day until the 14th month (when I ended tx), which was about a total of 6 months being fully undetected, and using sub-optimal Riba.  I was undetected for too short a period of time, AND very underdosed on the Ribavirin.  I relapsed in one month after ending tx.  No Procrit was being used at the time.  I also knew I would relapse, given those factors.

My second tx was using Peg-Intron, in the largest vial then available.  It worked out to almost twice the standard dose prescribed for my body weight, hence the DoubleDose moniker.  I used 1,200 mg./Riba, and saw very rapid drops in my red cell count.  By month three I was on full Procrit, and ended up doing it 2x/week, at about 60,000 IU total/wk.

The plan was to go for 72 weeks, and I did it with flying colors, of course feeling like I had been run over by several trains, trucks, and beaten by a street gang....other than that it was fine.  I did have a ton of all the notable sides, but managed to work (run a consulting business), go out, attend sports and school events with my family and kids, and eat lunch out with friends regularly.  Only a very few knew, and I pulled it off with everyone else, without ever letting on what was going on.  Some meetings were 'surreal', and I felt like I was going into another realm, ...but I got by, and made it to the finish line.  I have been undetected for well over three years now, since ending tx, and am glad I did what had to be done.

Its not all without a price though, since in my case, I have plenty of tx. after-effects, which is easy to understand with all the interferon that I subjected myself to during a five year period.  You have probably read my posts regarding post-tx problems, but that is another subject.  I will deal with those issues actively until I get some resolution, or at least an understanding of how to manage them more successfully.  Some may eventually subside, some may not.  That's part of the game, and not really totally unexpected.  I am just glad that I beat the virus, and it was all worth the effort, suffering, and expense.

I think you will also have success.  Best of luck in your next round!!!!

DD

[FlGuy]

First tx was a 'by the book' dosing by the doc. He has several hcv patients, but I don't know if he'd be in the category of 'whiz-bang hcv guru'. I'm a 3a did 24 with PegIntron/800 mg and relapsed after tx. Rested about 9 months and going again with 1200 riba and switched to Pegasys for 46 weeks this time. Double dosed the Peg for 1st 4 weeks (und at week 2) and took riba for a week before shot#1 to build up the riba in the blood.  This tx directed by 'one of those Univ. liverheads' but executed by same doc as 1st tx.  He agreed to follow liverhead directions. Weight wasn't an issue for me, but the formula for tx #2 is basically longer and stronger.

[Hepatitis Researcher]

You wrote:

My first question, is it possible that this result is in error? Am I wrong to want this confirmed by another test?

Chances are unfortunately quite low that this was a mistake. On the other hand, considering the important consequences, a repeat is not unreasonable. What would be of interest also is the dynamics of this "sudden??" increae from UND to 60000. Does it hold here? Is it the beginning of a spike? Is it the reflection of good power and specificity of the immune response to HCV that it stays this low? An "immune escape variant" with nevertheless low replictive fitness? The start of a real spike? A flare?


Q
. Is it possible that this is a spike that the immune system could handle? In other words, is it possible that these small spikes occur but are handled by the immune system or is this amount (66000) an indication that the battle is lost?

Response
The possibility that this is a short spike that will be spontaneously resupressed by your immune system is very remote.

Q
As to retx, losing weight is going to take a while for sure. My thought is that I would like to go back after this thing while its down. I dont like the idea of letting virus do more damage and making me harder to treat.

Comment
There is clear benefit by losing weight in terms of protecting your liver from accelerated fibrosis. It is less clear if your immune system will gain substantially more functionality against the virus in a re tx to justify the wait for the weight loss.

The options to increase the antiviral effectiveness of a retreatment regimen are numerous. Several have been mentioned by other very proper comments here. One has to understand the concept of SOC - that is registration trial derived - and the enhancements that daring hepatologists prescribe based on conceptual understandings and smaller trials testing some of these concept. One of these key concepts is that rapid, intensive supression of the virus in the beginning of TX - "induction therapy" - combined with highest possible riba dosing is a critical component of success since it rapidly removes from the virus the capacity to a mutational adaptive response. Thats also where the good starting dose of riba comes in. This mutational power has to be struck down with maximum force, combined with the idea, that whatever adaptive mutation might arise - we give the "newly forming adapted" virion a second and third push to mutate itself even further- through the riba -that will render its useful 1st idea useless. Thus combinations of NonpegIFN with Pegifns, hgher doses in the beginning, more frequent doses to keep the IFN concentrations up continuously are all used to maximize the chances for later SVR.
That early response and its importance is also reflected in the predictive power of early - week 4 - UND.
You said you were UND at week 4 - by which test? It makes a huge difference in predictive power if you are UND by a 400 copy or a 5 copy limit test.

After that critical initial phase, reducing the now " invisible" amounts of virus even further is obviously the goal of further treatment. IF the UND at wk four would mean no more virus in the body, then we could stop treating right then.
No, basically the longer and harder you hit the " residuals" the higher the chances for SVR become. But this comes to the point, where the pain and the cost have to be weighed against the incremental increase in chances for SVR and also the increasing chance to harm your body with Tx toxicities that might stay with you after tx. To what extent this post tx syndrome is caused by "residual viral stimulation of the immune system" or by an "overstimulation syndrome" independent of any remnant virus presence is unclear, but likely both pathophysiologies will tske part to a varying degree in each case.

DD I would like to discuss with you at some point in time the possible diagnostic and interventional possibilities that might be available for a "post intense TX hyperimmune syndrome" as you seem to be suffering from.

There are other options that slowly emerge at this point to increase rates of treatment success. Many think early combo treatments will substantially further reduce the " intial replicative defense mechanisms" of the HCV. Some Drs might be willing to prescribe an addition of Thymosin alpha right from the start - import for such purposes is legal I understand- or use - once we have more clear info on its potencies and usefulness- off label Alinia as a component of the treatment or even both. It has to do with risk, liability, cost and trust and how it relates to a particular patients history and situation. To use a " fully maximized" formula for SVR success likelihood based on conceptual extapolation of small trial results you would have to either be an MD yourself or find one where mutual closeness and trust is as good as inside a family.

As you can see from patients in this forum, some have used a "sledgehammer" approach to achieve SVR and are paying some price for that too. Addition of a lesser toxic HCV specific antiviral might make it possible to up the chances without such high and long term toxicity and/or further increase in immune stimulation. The Vertex drug might be one such addition, or the Polymerase inhibitors or even that strange drug Nitazoxanide that we are currently wondering about....
I personally do not believe that a nontoxic cocktail without IFN/riba is at this time at the horizon. Addition drugs - for higher SVR chances with lower sides - yes.

.

[Bill1954]

RTS- I agree that you'd be well advised to get a consult with an aggressive hepatologist. IMHO, most gastro's are equipped for standard-issue Tx; however for the hard-to-treat HCV population a hepatologist is probably in order. I'm currently treating with a doc out here on the West coast; where are you located?

In any event, take real good care, and I'll be watching for upcoming info from you. Best of luck with this,

Bill
----------------------

Elaine-

Good to 'see' you as well! How is Nick feeling? Has he goten a refferal  to UCD yet? I hope all is well for you both,

Bill

[cuteus]

I wish you would not have used the F word because I am not sure how to diplomatically mention a MH friend who calls herself the same word.  She felt it was a negative factor, and she WAS a geno 3.  Did tx for two yrs.  Has SVR.  There was a question of a possible breakthrough at month 9 or 11, the reason for tx extension.

I played with some words in the searching and using the word 'efficacy' brought studys and abstracts that i did not get before;
http://www.clevelandclinicmeded.com/hcv/treatment.htm#retreatment
http://tinyurl.com/y65knh
http://tinyurl.com/t96gc

this result is not as clear to me;
http://www.medscape.com/viewarticle/537731_Tables

it seems the retreatment group had the same svr rate  as tx naive?
too bad it does not state how much time elapsed bt treatments.

[Bill1954]

Sorry to hear about your relapse; I can feel your pain, big guy. I haven't been posting in here lately, but I saw your notes above and thought I'd weigh in on this topic. First, a little about me:

52 year old Caucasian male
Genotype 1a
Grade 2, stage 3.5
190 lbs
Diabetes M. type 2
Dx with HCV 12/04
Treated with Pegasys/ Copegus total 56 weeks, from 2/05 through 3/06.
Slow viral response at 12 week assay, so increased riba from assigned 1200 mg/day to 1800 mg/day.
Became undetectable to <50 IU by week 20.
Relapsed within 30 days post Tx.
9/15/06-begin re-treatment with Peg-intron 150 mcg/week, riba 2000 mg/day.

Now, the obligatory disclaimer; I certainly can't recommend this protocol, and if I did, it wouldn't come with any sort of authority. However, I'm more than happy to discuss my own Tx experiences with you, should you and your doctor decide to go this route.

At the beginning of my first Tx, I weighed about 240 lbs. Although I felt like hammered dog poo during the last session, I actually managed to gain weight, topping out around 255 lbs toward the end. As noted above, I had a slow response at the 12-week assay (missed the 2-log drop by 760 IU), and increased my ribavirin dosage to 1800 mg/day based on a number of factors. My Hgb was never seriously riba-challenged throughout last Tx, bottoming out at 13.2. Additionally, a small pilot study appeared in Feb 05 using high dose ribavirin with excellent results. Here's the addy:

http://www.hivandhepatitis.com/hep_c/news/2005/021105_a.html

And an excerpt from the study:

"...In the current pilot study, the objective was to evaluate the standard dose of peginterferon alfa-2a plus a daily dose of ribavirin that was individualized and calculated from a pharmacokinetic formula based mainly on renal function. In order to reach the targeted concentration of ribavirin in the blood serum, the study participants needed a mean ribavirin dose of 2,540 mg/day (range (1,600-4,000 mg/day). This equals more than double the currently recommended daily ribavirin dose...".

PLEASE keep in mind that this was a small pilot study, involving only 10 subjects: the results could therefore be construed as practically anecdotal However, as a stage 3-4, I felt that the risk-reward was there. My doctor had enough riba on hand to allow me to increase without involving insurance, but I relapsed nonetheless.

This treatment, I went into Tx dosed at 2000 mg/day. At my current weight of 190 lbs, this provides a ratio of 23.1 mg/kg.
Subjectively, I feel quite well so far; however, it's still early in the game. I'll do injection # 12 on 12/1, so there's plenty of time left for me to feel like cr@p, lol!

In terms of labs this time, my Hgb bottomed out at week five at 11.9; then rose slightly and stabilized/self-corrected around 12.2. The 4-week assay indicated undetectable per bDNA <615 IU, but detectable per TMA qual >5 IU.
The 8 week TMA then returned with undetectable to <5 IU. An additional note: my LFTs's never normalized during last Tx. ALT dropped to 72 at week 12, and then crept back up above 85 for the remaining treatment period. My doctor hypothesized that fatty infiltration (steatosis) might have been at play, although it wasn't mentioned in the narrative portion of the biopsy report. Having lost 60lbs + between treatments, this time my enzymes have been riding in the low to mid 20's.

That is my introduction; hopefully it answers some questions for you. Please feel free to bat this around with me if you like; I'm more than happy to answer any other questions that might arise.

Take good care,

Bill

[cuteus]

I must say, that you are truly a special case.  Not too many RVRs out there that are negative for a few months post tx, and come back as a relapse case.  Has your dr told you how unique your case is?  I can not remember many people in your case, if any.  Greg, from better angels post somewhere at the bottom of the page, was a similar case.  He was negative early, neg at EOT, and at 6 months post tx, and came back pos at the year mark.  I will never forget that post.  It was around that time I had done my 6 mo post tx PCR with the exact same test he did.  I was freaked out to no end.  Not a good follow up statistically speaking.  He finished his infergen tx and is now again neg at the 6 mo. mark.  I believe he started tx shortly after finding out the virus had returned.
I have been looking for hours for studies on how soon to retreat because I was helping another friend in the same situation as you, before I saw your post.

Nothing found so far.  I am going to try a different search engine than google.\
You are so correct in your speculation wondering what doses are going to work better than giving you a negative at wk 4? Your original tx did that, it gave you the RVR and svr until the 3 mo post tx PCR.  What can you change except the tx duration?  How to justify that? You were negative early.  ARGH! you are too unique!
the original riba and inf doses were enough to get you a negative PCR in the blood.

I would love to see a research group take you on, and test you for all sorts of immune cells responses, and for testing PBMC and other tissues for hcv presence.
I think you are that special.
But if not, maybe doing what Greg did, pick up the pieces and retreat, to finally get the svr for real, forgetting the dynamics of how and why it did not happen with the first round...
At Last... Infergen and Hope - Better-Angels: 11/16/2006

if you feel the urgency to get this behind you, due to liver damage or other personal reasons, and the first tx did not cause significant physical damage, then it is up to you how soon you want to get going again.
If I find anything relevant while searching for the other MH member in the same situation, I will post it here.

[returntosender]

Thanks for the help.  I always thought I was special and now I know it! LOL.  This is not quite the special I envisioned as it does not involve applause and shiny trophies.  Ya know, I just was reading Dr. Cecils thread - because he is so pro tx - and he said that once you get 3 months post tx negative you have 95% chance of success.  What the heck was it that happened to lose this thing.  I did have some major gum work after that 3 month PCR.  I wonder if all that blood somehow contained some active virus that worked its way back into the bloodstream?  Sounds crazy when I say it though.  

I also must admit that I wasnt living the healthiest lifestyle basically eating anything I wanted without a care at all.  Lost 40 pounds on tx and was working it back on.  Perhaps this stressed out the liver or immune system somehow.  Also, had some serious back problems for which I was given percocet and popped a fair amount of those - maybe Tylenol stressed liver and virus reemerged.  Find all that kind of hard to buy though because I didnt get the impression that SVR was all that finicky.  

At any rate,  I really really thank you guys for your thoughts.  I am ready to retreat tonight if I could.  My selective memory has all but blocked out my previous tx.  At stage 2-3 though I am somewhat reluctant to jump in too fast.  The first thing I am going to do is get another PCR.  The second is get a doctor who knows a bit more about using Riba on fat guys.  The third is to - well I dont know the third yet but I will soon - maybe it will involve that research team - that sounds good - I need a team working on this one. Perhaps its the fact the my second toe is longer than my big toe - I always thought that was a problem. LOL

[jmjm530]

You might want to reaccess your liver damage with a good hepatoloigst before making any decisions -- be it needle biopsy, fibroscan, fibrosure or some combination.

If you liver damage hasn't progressed, taking a year or two to get down to your ideal weight has a number of advantages. First, a lower BMI (body mass index) is associated with better SVR outcomes, as well as a slower progression of Fibrosis. But perhaps more important, if you're actually 100 pounds over your ideal weight, the health consequences of not losing that weight may be more serious at this point than the virus itself. Another reason to wait -- again assuming no fibrosis progression -- is to factor in the SVR trial data from VX-950 which will be flowing in all throughout 2007.

The alternative seems to be what some are calling the "sludgehammer " approach, be it high-dose riba, more extended SOC, infergen, something more experimental, or some combination. Perhaps if you weren't an RVR -- as HR suggested, check the sensitiviy of those tests -- the path might be clearer. But assuming you were an RVR, to me a future path is less clear.


All the best in whatever you decide.

-- Jim

[cuteus]

I meant to address your theories for relapse; dental work, pain killers, bad diet, etc  Not likely, your brain is telling you, and you know it is correct!
If I would have relapsed I would have been blaming the CTS release surgery, the dental work, the antibiotics, the champagne at daughter's wedding or the mojito, stress at work, driving too fast, flipping the finger too much, etc.  It does not work that way and you know it.  
HCV was still there, probably held back by some powerful t cells or something.  What finally let the dogs out, it is anybodys guess, most likely the super powers exhibited by hcv. But, it responds to tx, and that is the plus side. You know, since you are so unique, you could end up like pharoah, another member here.  Like you, negative through tx and at eot, negative also.  Post tx, he had two PCRs that showed a positive vl.  Then, the next PCR was negative and have been for two yrs.  What the heck happened in that case? another hcv puzzle.

[cuteus]

this list needs a bit updating, but it is a good summary, there might be another one out there and someone might have it bookmarked, but until then, this will do:
http://www.hivandhepatitis.com/hep_c/news/2005/ad/102605_a.html

[returntosender]

Thanks for your analysis - my 4 week PCR was a Quant Real Time PCR using Roche COBAS Taqman Analyte Specific Regeant which I believe measures to 75 copies.  To summarize your comments, I think you are saying that if another PCR is positive then retreatment may be indicated and that weight loss alone cannot justify the wait and that I should be looking for a doc who is willing to be more aggressive escpecially in the beginning of treatment but not so aggresive (aggressive) with the SOC that I will be damaged for life but more aggressive in terms of adding some of the newer safer regimes that are out there. However in order to get a doc to do this I have to have him in my family. Thats sounds pretty straightforward. LOL.   At any rate, thank you very much for the well thought out response.  You are such a great addition to this forum.  It is absolutely a blessing to have you around. Thanks again.

[returntosender]

You said you lost 64 pounds between txs.  Was this purposeful or just a tx side?  Do you attribute your improved LFTs to the weight loss?  After 56 weeks of tx, were your post tx sides gone before you started again in Sept?  Is your experience the second time around similar to the first in terms of sides?  Is the use of such high amounts of Riba something insurance companies definitely wont pay for?  

Cuteus - sorry about the "f" word, I rarely use it but it slipped out - lets just say I shop at the "Big and Tall" section of Sears.   Thanks for your research but it occurred to me that there will be no studies or guidance on my situation because, as you said, it is so unique.  Noone is going to retreat if they are clear at 3 months.  And usually if you are clear at 3 you are going to wait till 6 to retest.  So as a practical matter, noone who is in my situation would have ever gone back in before 6 months.  The guidance I have to find is for someone like Greg who relapsed after a year or someone who failed the 6 mos test. How long did they wait to retreat and how did they retreat.  Greg went back in with a vengence and lots of Infergen.  I dont quite have the stomach for Infergen and wonder whether it is necessary for me given my great reaction to Peg.  I have always cleared the virus with interferon, even when I first treated with it in 1996 - I became undet back then almost immediately.  I have always had problems maintaining the SVR.  At any rate,  I will probably have to be a trendsetter here blocking once again for other former football players seeking the goal line of SVR.  Once a lineman always a lineman.

[returntosender]

Hey buddy, didnt see your post there, thanks for your thoughts. Good to see you, hope you are well.  Dont worry my relapse wont rub off, I am having it stuffed to place on my mantle.  Your advice about waiting and getting health in order is good and certainly something I will consider.  Hope to see you around more, I always like seeing your comments here.

[jmjm530]

Child,

I'm doing fine, thanks for asking. Just trying to pick up my life where I left off close to two years ago. While never incarcerated, I imagine it's like coming out of prison or a Rip Van Winkle state. For me everything stopped when I started treating -- work, relationships, sports, activities, etc -- and just recently getting back.  I view this as very positive, almost like a re-birth.

Return,

Thanks for your well wishes and no worries here about "rub off". What will be will be. Just think you have a great opportunity/motivation to lose all that weight which can't be good for your general health. Additional bonuses would be a better chance of SVR plus by then newer drugs like Vertex may have proven themselves in trial. Of course this assumes that you're still stage 2-3. If things have progressed then the more agressive approaches might make sense. Take some time to think this all through and I'm sure the right course will present itself.

Be well,

-- Jim

[Bill1954]

From C-20 above:

"You said you lost 64 pounds between txs. Was this purposeful or just a tx side?"

Naw, that would have been to easy :-). I can assure you that the weight loss was intentional. Prior to treatment, I was told by two doctors that it was OK to put my diabetes control on the 'back burner', with Tx becoming the priority. I stopped testing my BG during treatment, and allowed my sugar to rise to unacceptable levels. When I began checking again after completion of Tx, I was shocked to find that my fasting BG levels were above 300 mg/dL (ref range 70-120). So, after reviewing the facts: out-of-control blood glucose, possible fatty infiltration of hepatic stellate cells (steatosis), post Tx relapse of HCV, and a host of other reasons I decided to put down the snickers bars and lose some weight. Diet modification including portion control took care of quite a bit, but I needed to get some much-needed exercise going to help out with the remainder.

"Do you attribute your improved LFTs to the weight loss?"

Boy, that's a tough one to answer. As I mentioned above, my doctor hypothesized that steatosis might have been at play as a separate but parallel process to HCV. However, after 56 weeks of Tx I might have experienced improved liver histology. The doctors were hesitant to re-biopsy between treatments because I obviously intended to re-treat ASAP. For what it's worth, I was initially diagnosed with hepatosplenomegaly per ultrasound. Another subsequent U/S between Tx showed a marked reduction in spleen size, suggesting improved liver architecture. As to your question, I'm sure that losing a few pounds didn't hurt the liver any, but there are too many factors at play to consider.

"After 56 weeks of tx, were your post tx sides gone before you started again in Sept?"

RTS, my post Tx sides were almost non-existent. Although during the initial treatment I experienced a 4-month bout with GI issues, including moderate to severe diarrhea; and the typical depression associated with IFN, they pretty much disappeared within 5-7 days after my final ribavirin, and I was 100% within three weeks or so.

"Is your experience the second time around similar to the first in terms of sides?"

Simply put, this 2nd round has been a breeze so far. At 12 weeks into treatment, I'm happy to report that the sides are minimal at most. Honestly, if this is bad as they get, I could see doing this indefinitely if necessary. However, I've switched from Pegasys to Peg-Intron for this Tx, so that might have made a difference too. I'm actually off label with the Peg-Intron as well. Although my assigned dosage is 150 mcg/week, I'm on record with my doctor for "squeezing" the Peg-Intron vial; in other words, by injecting the full syringe instead of the directed .50 ml I'm able to draw up about .68 ml for a total of 202 mcg/week. This requires the use of vials; I don't think this is an option available with SP's Ready-Pen.

"Is the use of such high amounts of Riba something insurance companies definitely wont pay for?"

From what I gather, the insurance co's (and their actuaries) are beginning to soften up their position on off label riba dosing. More and more doctors are prescribing 1400 and sometimes 1600 mg riba in an effort to achieve therapeutic plasma concentration for us big boys. Although I believe I'm the highest dosed patient my doctor has, the insurance approved with no questions asked. That said, the same insurance co denied my request for 1800 mg last year, so go figure. If you and your doctor choose to go this route, you might plant the seed in your doc's head in advance that he might need to write a letter or two on your behalf. My doctors strategy is to play fair with the first request, then if a letter of denial shows up, he has staff that absolutely *bury* the insurance co with studies, some which are relevant and some just to add bulk; he says that quite often does the trick ;-).

Hope that helps a little, and again, feel free to run any further questions by me if they arise. I'll try to watch for your posts. Again, take real good care--

Bill

[sfbaygirl]

I noticed you have the same exact PCR I did. Pretty poor! 75IU is like 200 copies, so you really don't know if you were UND to a low amt. with that test. I was fooled as well. HR mentions another good test, not sure my ins. will cover it, but I plan on getting one, even though I may have to pay. HEre PCR's are $250. Not sure about the most sensitive....

Also, I know that dental work can release bacteria and maybe virus. My x had to take antibiotics when he went to the dentist after having a heart valve infections years earlier.

[DoubleDose]

I would very much like to hear more from you about possible therapeutic modalities for the 'post-tx hyperimmune syndrome' as you described it.  You are right, some of us used the sledgehammer approach to therapy, and for me it was because I literally had to.  My VL was slow to reach undetected in both tx'es, and in the first led to ever increasing amounts of interferon (and varieties), almost to the point of absurdity....but I really was the one pushing all the way for the most radical approach possible.

On the 2'nd round I used the most inf. that I could squeeze from every vial of Peg-Intron (using the largest vials available as well), and went the full 18 months, limping to the finish with Procrit and full Riba, etc.  So I was not shocked to see the plethora of post-tx syndromes develop, although part of me was hoping for a blissful, 'feel-great' state of SVR, where everything would work properly again, and I would be rejuvenated.  Of course it was anything but!  (Oddly, for about one month after ending tx, I felt better than I had in 30 years, almost symptom free!!!!)

So, indeed I would like to know what others in my 'boat' might be doing to mitigate the effects of all this immune system over-stimulation.  I feel like the poster child for 'wastebasket' autoimmune disease, without any specific label to hang on it, and no doctors with any really practical answers, much less treatments!  The rheumatologist acknowledges that the inf. tx often provokes this 'autoimmune' type syndrome, and then says 'keep an eye on things' take care now....

If you know of any approaches that seem to be of help, please do let me know.  I fear doing anything that might 'retard' the immune system, knowing that the few late relapses out there seem to have come from that very same type of medical treatment.  I also am concerned about ongoing immune system over response eventually leading to issues like lymphoma, or MS type illness....as well as the expected issues like Lupus, or similar AI type diseases. I continue to experience a mild parotid swelling, that is chronic, and always there. (like Sjogren's)

Thank you for your interest and all the time you have spent responding to our forum members.  I like to think we are all working toward advancing the knowledge base relating to HCV and its treatment.  With community efforts, often 1+1+1+1 can end up equaling 16 rather than four.  Pooling all our inputs, and experiences, while not pure empirical science, still can unearth new insights.  Thanks for being a part of the discussions.

Any feedback on the post-tx issues will be welcomed!

DoubleDose

[jmjm530]

DD:If you know of any approaches that seem to be of help, please do let me know. I fear doing anything that might 'retard' the immune system, knowing that the few late relapses out there seem to have come from that very same type of medical treatment.
-----------------------------------------------------------
Could you please expand/clarify what you mean by "doing anything tht might 'retard' the immune system". Are you talking about drugs, alcohol, diet, what?

What "few late relapses" are you referring to? Are these post SVR relapsers? And if so, are you talking classical relapse, i.e serum negative to serum positive, or are you talking about finding virus in compartments other than serum post SVR?

I mention this because it still appears that relapse -- as defined by finding virus in serum -- after SVR is quite rare.

All the best,

-- Jim

[Better_Angels]

Boy these are difficult decisions, not like what's for dinner tonight?

Greg retreated within weeks of his relapse. His VL came back at only 3,000 so his doctor immediately ordered another PCR and it came back at 100,000+, clearly it was on the upward move.

Greg was very aggressive in retreating, not really sure why, I think those are thoughts that only run through the mind of the person who is faced with having to make the decision. He's a quiet man, didn't say a lot about it or why he chose the Infergen and the dosing strategy. We did discuss options but in the end he seemed to have his mind made up. Greg did say that once he had made the decision he felt better about doing it, I guess getting your mind made up is the hard part.

We think improved liver histiology, low VL and quick aggressive retreatment led to this undetectable status. That's just a guess though. He did just get his 6 month PCR back (this time we waited 26 weeks to do the test rather than 24 weeks) and of course, we are cautiously optimistic since he relapsed at 1 year last time, but our hope is that it couldn't happen twice.

I wish I had some words to help you. Just know that so many care.

Hoping for you and yours,
Debbe

[DoubleDose]

I am of course referring to the couple of cases that were highlighted in the HCV medical press in the past few years where patients were placed on immunosuppressive medication therapy for other disorders, and saw a full return of the HCV virus in their blood and liver.  I think one person was an SVR for over 8 years, and had documented PCR negative blood tests many times over the years since their SVR.  The other was a similar case where the person was a 7 year SVR, and saw the virus return after doing immunosuppressive therapy.

Now some of the doctors that I know would interject that maybe these persons were somehow 'reinfected' with HCV, but that seems to be a very weak response to me.  Both cases were identical, and both individuals redeveloped the HCV viral positive state, by PCR, after immunosuppressive therapy. In your wildest dreams would you think that these two people, many years SVR would be playing around with HCV infected drug equipment....and doing immunosuppressive therapy to boot???? In my book, that is a relapse.  These cases also demonstrate the concept that the virus goes into 'remission' after SVR, rather than eradication.  Both cases should be fully investigated by the HCV medical community (if they are interested in really knowing) in order to validate or to cast doubt on the viral persistence/remission theories that have become popular.  If they see reason to question the relapses in question, then I would like to hear what it is!  I have heard nothing to the contrary from any HCV experts to date.

I do believe that Mike Simon recently dealt with a minor episode of this sort of viral behavior, where immunosuppressive meds caused a flare of the virus in the liver,after being SVR, for him.

DoubleDose

[jmjm530]

Thanks for the clarification.

In Mike's case, I believe he was detectible only by special tests done on liver cells, not by tradtional serum VL tests. RTSs post was somewhat disconcerting as he apparently relapsed after being non-detectible 3 months post treatment by Heptimax. He mentions some dental surgery as a possible cause. I have a tooth implant procedure coming up and while my rational mind says no problem, I'm playing around with the idea of delaying it until I've been viral negative for at least a year. Right now It's nine months.


-- Jim

[cuteus]

8 yrs ago the PCR tests were not as sensitive as today's.  Snook man has reported a few negative PCRs throughout the yrs, when in reality he had a very low VL that was not detectable by the tests of those days.  It could be that with some folks, the vl remains extremely low, and thus they are not truly SVR. One theory. A more sensitive qualitative test might have shed light as to the presence of continuing infection.
As for Mike, it was the reduction of immunosuppresive medications, not its introduction, that induced elevated enzymes which led to liver tissue testing that produced a positive result.  He mentioned that his immune system activation by the antirejection drugs reduction is what elevated his results.  SO it does not seem to follow the same pattern as the late 'relapsers'.

[jmjm530]

It's always a little unsettling when something that "should" have happened doesn't. RTS "should" have been non-detectible at six months based on being non-detectible at 3 months. They correlate very closely, but still not the same thing.

If RTS had said he relapsed 3 months after SVR (the nine month mark) then that would have been really unsettling since it would challenge the durability of SVR.

I remember emaling my doctor that I was about to pop the cork after my 3 month post tx SVR. He emailed back that I shouldn't celebrate just yet. I guess relapses between the 3 and 6 month post mark, while unusual, do happen.

I'll see about delaying that dental surgery as I'm only about three months from the 1 year mark. I think my chances of relapsing after that are worse than being hit by lightning.

-- Jim

[friole]

As another recent 1a relapser I am reading your answers to RTS with heightened interest.  If I read correctly, the most effective way may be to use non-pegalated interferon and increased riba if necessary to achieve rapid intense suppression.

I started with 1.52 million IU/mL.  At 4 weeks it was 2820 IU/mL and at 12 weeks 40 IU/mL (QuantaSure sensitive to 2IU/mL). My first UND by sensitive PCR was at week 20 (QuantaSure) (had a UND test at 16 weeks but it was only to <50) and was clear throughout the rest of a 56 week treatment.  My 3 month PCR was 680,000 IU/mL (QuantaSure). (100% compliant)

My start weight was 173 and I took standard Pegasys and 1200 mg Ribavirin (Copegasys until switched to generic by the insurance co).  My weight dropped as low as 153 during tx so I was overdosed for the riba most of tx.

Now what?  My SOC GI will suggest daily infergen (appt on Thurs).  I have an appt with a hepatologist in Dallas in April.  Should I wait to confer with the hepatologist?  Should I try infergen now?  Both my ANC and HGB dropped during tx but I didn't have many of the severe side effects I hear others refer to and suspect I was underdosed with interferon.  I am trying to gather all the information I can before Thursday's meeting.  By the way, my biopsy was G1/S1.
frijole

[Eisbein]

As far as I remember, the women that became PCR pos after 8 years being undetected, shortly afterwards became neg again and has remained neg. She also had a condition called hypergamma something.

I am not certain that was the case you are referring to.

Ivette, we just talked about that case. Anything else you can remember?

Ina

[sfbaygirl]

When did you relapse? I know it wasn't long ago. My take is to hit the virus again before it has a chance to flare up again. Therefore causing less fibrosis etc. I don't think I would wait until April. Not meaning I wouldn't go to that appt., but if your VL is low now hit it now! just my two cents. I am probably in the same boat and still wondering about extending....rather than doing it again.

[friole]

My last riba was 08/11 and the 3 month PCR was 11/3.  I can get into the specialist in February - that is her earliest appointment - I just chose to wait until after my busy time at work.

As for hitting it hard while it is low - that is what I want to find out -- if it makes any difference to start right away or wait.

You were not clear at 10 weeks, right?  I would consult with a specialist right away (I think you are doing that, aren't you)

[sfbaygirl]

Yes, I have a tentative appt. set for the beginning of Dec. From all I have heard and read, it would be best to tx while the VL is low and before you have a flare up. From hearing here about many VL flares, higher than before tx, after tx ends when the immune system is weakened it seems it would be best to get to it while low for a better chance of SVR. Why don't you ask HR. He explained it to me, but I dont' want to mess it up!

[FlGuy]

Just a thought, not a suggestion.  If you go for more tx I imagine it would be for more than a year.  How many consectutive tax seasons could you do on tx?  Actually, it's a question, not a thought.  Take care Kathy.

[Hepatitis Researcher]

The notion that treatment at a lower vl has better chances for success is  alogical and accepted one. And beyond that, as I outlined above, there are conceptual enhancements to the SOC like "induction" therapy that are sometimes being used by individual HCV treaters - they come also with increased pain, risk, and expense.While some of these enhancements have been tested in small trials, the participant numbers are usually too small to allow firm enough conclusions to add them to the SOC.SOC also takes off the burden of responsibility for such treatment enhancements/variations from the Dr. so it is understandable that most just stick with it. It is always some game of chance with very high stakes and noone wants to take the blame for a negative outcome.

[friole]

I can't do any more tax seasons on tx -- or at least I think I need this one year break.  Then If I start in May 07 I would only have one tx during tax season.  I am going to ask for that PCR to see if the vl is rising or stable.  When they say hit it when the vl is low - I am just not sure --680,000 almost a month ago - may be more now -- just doesn't see all that low.
kath

[returntosender]

Kath - Ditto for me on tax season but with these automatic extensions going to Ocotber now, it seems that tax season never ends for me. LOL Besides with all our estate and trust work coming on fiscal year ends, the tax season really doesnt end.

One thing I read that might be relevant to our situation, and that I mentioned in another post, not sure if you saw it, is a 2001 study by Shiffman regarding the use of Riba at the end of a combo therapy.  They treated relapsers with Riba/Pef for 24 weeks and then stopped half and continued half for another 24 but only with Riba.  The Riba continuance did NOT result in any additional benefit or SVRs.  Additionally, the anemia of patients resolved when using Riba alone, leading Shiffman to the conclusion that Interferon - in its effect on bone marrow - was the main culprit for anemia.  

What I get from this article, which I hope you will read for its direct assessment of relapsers,
http://www.journals.uchicago.edu/JID/journal/issues/v184n4/010102/010102.html
is that continued treatment for those who relapse is quite successful (50% success) even if it only lasts 24 weeks.  I also get that Riba is not useful as an monotherapy even if it is used at the end of tx on a nondet. patient.  Also, Riba and anemia are not the partners that people think they are and therefore, looking for anemia as a measurement of Riba dosing seems unfounded.

Since I came so close to SVR I am inclined to ask the BCLD, after April 16, 2007, about treating with additional Peg and the same amount of Riba for 24 weeks.  I am concerned about going too long on tx which for me is any longer than 24 weeks.  Since I just completed 48, I pretty much know that adding an additional year or two is asking for trouble with this stuff and I am barely recovered from my previous tx.  

By doing 24, I give myself a half decent chance to clear. I am exposed to the drugs for less time.  I can monitor things very closely with monthly PCRs and if I clear the virus within 4 weeks or get a 2 log drop within that time, on one of the ultra sensitive PCRs, then I do 24 and stop.  If nothing else, I get an additional 6 months of no virus and get an additional chance at success with less chance of permanent sides and that much closer to the new drugs.  Maybe I can add some agent like Alinia to the mix as well as was suggested by HR.  What do you think of that taxing strategy?  

[FlGuy]

Good luck in whatever you decide.  The time between tx1 and tx2 was great for me.  I felt great, was energetic, rejoined the the human race and the family like me again. So, if it's in the cards that you sit on the sidelines for a while - enjoy it.  As you've read there are several re-tx approaches that you can take but my suggestion would be to get yourself as physically and emotionally healthy as you can and get hcv out of your head for a while (to the extent you can).  At least it sounds like your becoming reconciled to the situation.

[friole]

FL -- ha ha -- get HCV out of my head???  How the heck do you do that?  I fear it is here to stay, my friend.  Physically I feel real good right now.  Last night, as I was laying on the couch sleeping thru a tv show (Studio 60) I was thinking I really missed the anemia that allowed me to do that every night.  Now how stupid is that?  I think what I was missing was the false comfort of curling up and having a reason for it. Does that make sense?

Return - know what you mean about the extended season.  We were busy until October, and we do a lot of estates and trusts too but most are calendar.  Still, with the age of our clients I anticipate a 706 or so this next year.  I could have gotten in to see the specialist in February but opted for April 23rd.  I hope that isn't a mistake, but I really don't want to start right back up.  

I read the study.  Interesting. Table #3 was very good.  What I got out of it was anyone with over 2 million copies and genotype 1 who wasn't clear at 3 months (like me)- even with extended time - had less than a 50% chance.  So the hard part would be to get UND by 12 weeks and I don't think that would happen with me unless I bumped up the INF or did non-pegalyted daily.  It is an interesting thought, tho to only do 24 if I can get UND by 4 or 12. Thanks for the link
kathy

[FlGuy]

For what it's worth...double-dosing Pegasys for the first 4 weeks this time was not as bad as I had expected. TX#1 was peg-Intron and the double pegasys was about the same as single PegInrton for those 4 weeks. As you know, people react differently to the pegs so there's risk of feeling like real doo-doo. The key does seem to be und asap and then ride it out. Back-burner stuff though, enjoy the break.

[DoubleDose]

I am concerned about your strategy.  I will be very straight forward in my opinion, for whatever it is worth.  I think that going 24 weeks after relapse is a very 'iffy' plan, with little to support it.  If your current relapse has indeed taken you back to full scale chronic infection, then you need to get clear first, and use the appropriate amounts of tx drugs and length of tx to achieve SVR.  This will doubtless mean much more on the Riba side.  

Also, though the interferon truly does contribute a good deal to the anemia, the Ribavirin is also well proven to be a major culprit as well.  It can be demonstrated during tx, when red cell counts are falling to dangerous levels, just decreasing the amount of Riba usually brings the red cell count right back up.  Procrit is there for these issues, and the Ribavirin needs to be affecting the plasma hemo. counts pretty aggressively, for it to have the desired effect, and prevent relapse by sufficiently genetically scrambling the remaining viral copies.  

I also honestly believe that you will need to do an extended tx to be on the high probability side of the SVR curve.  I have seen and heard about far too many cases of relapse from just not going long enough.  A friend on his second tx went 18 months, and relapsed.  He did a full 2 years on his third attempt, and has now been clear for over 20 months after ending his third tx.

I would be very careful about assuming that a 24 week course is going to do the trick for you, without lots more study findings to support this approach.  I understand your concern about the length of tx and long term sides, but I would not let that concern dictate your therapy.  I really do not believe that you would want to go through another relapse.  If you just take it week by week, often you can cover great distances without all the stress of thinking about how much total time must be done.  

Good luck, and really spend some time with a highly experienced HCV doc. who has been through this issue many times before with his own patients.  And one who has been successful in getting them to SVR.

Best wishes.

DoubleDose