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

[child24angel]

As of right now , we are playing the waiting game.  In between insurnace.  He is waiting for GHPP to help us.  Thank you for asking.



You sound so good.  Tx must not be that bad right?

Are you still running everyday?  I hope you keep us informed how you are doing.  If I read it right above are you undectabable right now?  I sure hope so Bill.  I wish you the best.



Elaine

[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.