Aa
HR - Question about retreatment
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.
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.
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.
MEDICAL PROFESSIONAL
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.
.
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.
.
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
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
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.
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.
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
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
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.
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.
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