Aa
Do chances of SVR increase with each UND during tx?
A few weeks ago, Goofy and I were discussing, at lunch odds of SVR going up as each UND PCR was achieved at lunch. I wondered if our odds go up as we stay this way, as it seems odds should go up. Goof said he thought that odds of SVR would increase too. He told me (correct me if I am wrong Goof!) that since some people stopped tx, didn't achieve UND at various points, that perhaps odds would go up for us that do, as the numbers of people txing change. If say 100 people started tx and 20 had stopped or were not UND, our chances in those 50% numbers would increase as tx went on. Of course I love this theory and I wonder why we don't hear much about our increased chances (if there are) and what you guys think about this? Of course Goof was speculating, but it sure sounded reasonable to me.
Don't know about any improvement from the first round. My visit to the U of M was a one-time event, insurance doesn't cover me there. I was hoping to get a Fibroscan there - but didn't work out. Maybe when tx #2 is done Fibroscan will be more ready for prime time use/availability. I'd do another bx, but I'll wait that out too. Doc thinks 'longer and stronger' (1200 mg vs 800 and 48 vs. 24) tx will get it this time. Thanks
Not considering maint at this time. I'm restarting combo (pegasys and 1200 riba) in a couple of weeks for a 48 week stretch. Replapsed geno 3, early cirrhosis. I'm just thinking of options that may be available later on. The doc at UM (diff doc, but where Snook goes) gave me the option of peg maint, but I decided to go the whole route at least one more time before I consider maint. Thanks.
Rev went from a stage 3/4, borderline cirrhotic, to a stage 2...
So yes, he did see excellent results.
So yes, he did see excellent results.
Thanks.
When you went to the 90 mcg peg, how were those couple of days after shot night. Were you fully function or were those 'wasted' days? Able to do stuff around the house, stay physically active that kind of thing? Ever get any proof of liver reprieve or recovery - like another bx?
When you went to the 90 mcg peg, how were those couple of days after shot night. Were you fully function or were those 'wasted' days? Able to do stuff around the house, stay physically active that kind of thing? Ever get any proof of liver reprieve or recovery - like another bx?
You said you relapsed after being UND for 88 weeks of treatment. When did you relapse after treatment?
Beagle
Beagle
No, a 4 week PCR study wouldn't be pertainent to me, but it could be for others. It is good to know how much better our odds are if we get UND at 4, 12, and 24 weeks, or in my case 12 and 24. I would like to think my odds of SVR have increased. Since I didn't have that sensitive test, now I don't have the option of even knowing what is was and knowing if my odds improved.
Saying all of this, I am just curious about it all. I know I can't change the past tests or not having biopsy. So I will never really know. But it is an interesting thought to me.
Saying all of this, I am just curious about it all. I know I can't change the past tests or not having biopsy. So I will never really know. But it is an interesting thought to me.
Does a PCR go to a sensitivity of <5 or is that a TMA?
Also, does anyone know to what the sensitivity a b-DNA test measures?
It seems from recent readings I've done that we toss PCR around a bit too generically and that we rarely differentiate between the actual method used or whether the test is qualitative or quantitative. The result seems to be comparing PCR numbers which actually appears to be more liken to comparing apples to oranges in some cases.
Then again, is it really necessary to split hairs that fine? From one study on TMA I read, it would seem so because some folks which achieved UND using PCR and relapsed and the very same sample tested using TMA and found UND was not achieved.
Does it increase chances of SVR? I would guess so if one is using the results to determine actual length of tx.
Also, does anyone know to what the sensitivity a b-DNA test measures?
It seems from recent readings I've done that we toss PCR around a bit too generically and that we rarely differentiate between the actual method used or whether the test is qualitative or quantitative. The result seems to be comparing PCR numbers which actually appears to be more liken to comparing apples to oranges in some cases.
Then again, is it really necessary to split hairs that fine? From one study on TMA I read, it would seem so because some folks which achieved UND using PCR and relapsed and the very same sample tested using TMA and found UND was not achieved.
Does it increase chances of SVR? I would guess so if one is using the results to determine actual length of tx.
I believe what the studies are proving is the EARLIER you achieve UND...THAT is what increases your odds and if you are UND at week 4 compared to 12 that is the big difference.
Of course things like the quality of the testing sensitivity have to be included as well in factoring any of it. Being UND to like 615 compared being UND to 5 --- is a big difference if you know what I mean.
So I don't really think it's how LONG you stay UND that increases your chances...because obviously that is the goal once you achieve it - and it's the EARLIER you are able to get there that matters.
Of course things like the quality of the testing sensitivity have to be included as well in factoring any of it. Being UND to like 615 compared being UND to 5 --- is a big difference if you know what I mean.
So I don't really think it's how LONG you stay UND that increases your chances...because obviously that is the goal once you achieve it - and it's the EARLIER you are able to get there that matters.
Sorry to hear about your relapse, that has to be tough. What sensitivity test did you have during tx and after? Since PCR's do not go to a 0 Vl, everyone has a chance of a few little buggers coming back out to replicate. Besides the virus that may be hiding out and decide to come out.
Yep, I am a responder and am very happy that the tx is working. I just hate thinking about that 50% chance of relapse while going through this awful stuff.
Flguy; Gotta go to the hemo today for Neupogen. I WON'T do that 'lasta anymore, unless the sx are the same on neup. So I may be whinning tomorrow! Hope not!
Yep, I am a responder and am very happy that the tx is working. I just hate thinking about that 50% chance of relapse while going through this awful stuff.
Flguy; Gotta go to the hemo today for Neupogen. I WON'T do that 'lasta anymore, unless the sx are the same on neup. So I may be whinning tomorrow! Hope not!
It's experiences like kespr's and my own that don't give me much 'percentage' inspiration. On the other hand, there are people like Amommy and Rifleman who are the poster children for tx optimism. HCV is too fickle to pin a lot of hope on. Glad you've been getting to the games - late summer eventings in the ballpark, what a life. Don't be jumpin' into any coves though.
Nothing like Indian Summer in SF. I feel really good, but don't feel like jumping in any coves yet. LOL
I understand your and kespr not believing in odds increasing for SVR given your history. But as you know half of us will relapse with a 50% odds. Tx might feel more worth it, if the odds of SVR improve as we get UND's along the way.
NY; I wonder what odds of SVR there are if you achieve UND at week 4. I bet they have to be better than the 50% we now have.
I understand your and kespr not believing in odds increasing for SVR given your history. But as you know half of us will relapse with a 50% odds. Tx might feel more worth it, if the odds of SVR improve as we get UND's along the way.
NY; I wonder what odds of SVR there are if you achieve UND at week 4. I bet they have to be better than the 50% we now have.
In my case I didn't have the better pcr test that test to less then 5. I didnt know I had options when getting tested.
It's not how many times you have an UND test - the important one is the first one, when you get there.
As far as I understand it...that is the big wheel of the deal.
The odds for a "cure" are ALWAYS really 50/50 no matter how you want to slice it up. Of course....we WANT to think well I have had UND at 12, 24, 36, 48 so my odds must be 90% in our heads..........
But I don't think they could INCREASE with each test because you could do a 4, 8, 12, 16, 24, 32, 40, and 48 or a 2, 4, 6, 8, 10, 12, 14, 16, 18, ........... why would that change the odds?
Geno 1 is 50/50. Trying to make any other sense out of "odds" is just making your mind spin around.
But.........we've all done it.
As far as I understand it...that is the big wheel of the deal.
The odds for a "cure" are ALWAYS really 50/50 no matter how you want to slice it up. Of course....we WANT to think well I have had UND at 12, 24, 36, 48 so my odds must be 90% in our heads..........
But I don't think they could INCREASE with each test because you could do a 4, 8, 12, 16, 24, 32, 40, and 48 or a 2, 4, 6, 8, 10, 12, 14, 16, 18, ........... why would that change the odds?
Geno 1 is 50/50. Trying to make any other sense out of "odds" is just making your mind spin around.
But.........we've all done it.
GO; I have wondered about those tests as well...It would be good to know the differences, not just blindly go to the lab with your PCR lab slip.
There are most likely no studies that show increased odds of SVR during UND's. But I find it is interesting...I mean once someone drops out of tx, you would think the odds would improve for those still txing...just something to toss around.
There are most likely no studies that show increased odds of SVR during UND's. But I find it is interesting...I mean once someone drops out of tx, you would think the odds would improve for those still txing...just something to toss around.
These are the only stats that I know of that have been done in a study. It proves that the EARLIER the response - the better and not how LONG you KEEP it.
THAT is what increases your odds.
TeraViC-4 targets patients with chronic hepatitis C who do not have very early virological responses after week 4 of therapy (no viral response at week 4 after initiating Pegasys/ribavirin therapy= detectable serum HCV RNA >50 IU/ml PCR). The study evaluates the risk:benefit ratio of extended duration of therapy, balancing increased response rates and adverse events.
Sustained response rates of pegylated interferon plus ribavirin, the standard of care for HCV, has produced overall sustained response rates of about 54% in phase III multinational clinical studies.
Analysis of data from these studies shows an absence of an early response, makes it highly unlikely (predictive value 97%) that patients will achieve a sustained virologic response. An early virologic response is defined as undetectable HCV RNA or >2 log decrease in HCV RNA (viral load) by week 12.
THAT is what increases your odds.
TeraViC-4 targets patients with chronic hepatitis C who do not have very early virological responses after week 4 of therapy (no viral response at week 4 after initiating Pegasys/ribavirin therapy= detectable serum HCV RNA >50 IU/ml PCR). The study evaluates the risk:benefit ratio of extended duration of therapy, balancing increased response rates and adverse events.
Sustained response rates of pegylated interferon plus ribavirin, the standard of care for HCV, has produced overall sustained response rates of about 54% in phase III multinational clinical studies.
Analysis of data from these studies shows an absence of an early response, makes it highly unlikely (predictive value 97%) that patients will achieve a sustained virologic response. An early virologic response is defined as undetectable HCV RNA or >2 log decrease in HCV RNA (viral load) by week 12.
In patients who were HCV RNA positive at week 4, there was a significant difference in the maintenance of viral response rates during followup. In those treated for a total of 48 weeks, the viral response rate declined from 61% at completion of treatment to 32% at the end of followup. In contrast, the viral response rate declined from 52% at completion of treatment to 45% at the end of followup in those who received a total of 72 weeks of treatment.
It's all based on 4 week PCR but the best I can find for you.
It's all based on 4 week PCR but the best I can find for you.
"Analysis of data from these studies shows an absence of an early response, makes it highly unlikely (predictive value 97%) that patients will achieve a sustained virologic response. "
This entire statement hangs upon what is the definition of "early response"? Most studies I have seen show that the VL drop is expected to be exponetial. Thus, a *very* large drop at the beginning which tampers to a decreasing rate of VL drop as tx progresses. This is what has led to the 2 log drop expectation in the first 12 wks of tx. So, if one shows such a response is it considered an "early response".
In my case, a drop for 72,000,000 to 2,400,000 in the first 8 wks would seem to be a substantial drop, but would it constitute an "early response", especially given that riba dose was cut in half 4 wks into tx? When I look at the fact that VL went from 2,400,000 to 1,800,000 from wk 8 to wk 12 it would seem that the exponential curve was not followed and that concentration of riba does play a very significant role in chances of UND by allowing IFN to killing virus and preventing it from replicating during the onset of tx.
This entire statement hangs upon what is the definition of "early response"? Most studies I have seen show that the VL drop is expected to be exponetial. Thus, a *very* large drop at the beginning which tampers to a decreasing rate of VL drop as tx progresses. This is what has led to the 2 log drop expectation in the first 12 wks of tx. So, if one shows such a response is it considered an "early response".
In my case, a drop for 72,000,000 to 2,400,000 in the first 8 wks would seem to be a substantial drop, but would it constitute an "early response", especially given that riba dose was cut in half 4 wks into tx? When I look at the fact that VL went from 2,400,000 to 1,800,000 from wk 8 to wk 12 it would seem that the exponential curve was not followed and that concentration of riba does play a very significant role in chances of UND by allowing IFN to killing virus and preventing it from replicating during the onset of tx.
I hope I can state this properly. I feel that length of time the disease lives in your body as well as the amount of damage could have a strong bearing on relapse after a few mo. undetected (post tx). The virus may find places to hide out that are damaged and not recieving blood circulation as it should to move along the virus or deliver the piosons to it. As the liver regenerates, the circulation could improve but very little of the poisons would be left to knock off the little buggers and Presto! relapse from a HEALTHIER liver. Just my guessing, have too much time on my hands lately.
I think that they presented the odds in the Sanchez Tapias study.
That had the odds of how much a 4 week UND PCR does for you.
I'll have to see if I can find it again. Between the Berg Study and the Sanchez Tapias study information - that is how and why I decided to go for 72 weeks as both studies had to do with me and my situation (ie: not UND at week 4 or 12 etc.)
I think the key to all of this is finding the studies and then seeing how they apply to YOUR case - they can't be applied in an overall general way because for example someone who IS und at week 4 is not the same as someone who is NOT.
So its important to use ALL of your information when making any decisions - and not just say well the study says.....
Know what I mean? I mean who cares what a study says if it's not relevant to your pertinant info.
That had the odds of how much a 4 week UND PCR does for you.
I'll have to see if I can find it again. Between the Berg Study and the Sanchez Tapias study information - that is how and why I decided to go for 72 weeks as both studies had to do with me and my situation (ie: not UND at week 4 or 12 etc.)
I think the key to all of this is finding the studies and then seeing how they apply to YOUR case - they can't be applied in an overall general way because for example someone who IS und at week 4 is not the same as someone who is NOT.
So its important to use ALL of your information when making any decisions - and not just say well the study says.....
Know what I mean? I mean who cares what a study says if it's not relevant to your pertinant info.
I've heard the same explaination that Morgaina gave as part of the rational behind doing the 6 mo and 2 yr post-tx VL tests. The other part, besides hiding in parts of the body outside of our blood, was that because no test measures to 0, the virus could still be present even in the bloodstream and replicate.
Regarding the action of Ribavirin you might find this interesting.
From:
<A HREF="http://www.medscape.com/viewarticle/543530?src=mp/">Viral Kinetics in the Treatment of Chronic Hepatitis C</A>
"Kinetic parameters were also studied when ribavirin was used in conjunction with pegylated IFN.[44] In this study, it was hypothesized that ribavirin served as an immune modulator. To account for this effect, the basic kinetic model also included an additional term called an inflation factor that had an impact on the rate of loss of infected cells after an initial delay. The study confirmed the observation that ribavirin had little impact on the first-phase viral decline, but increased the second-phase viral decline, when IFN effectiveness was low. A third phase was also noted, which may represent an enhanced loss in the rate of infected cells.
A recent study that modelled the impact of ribavirin on IFN therapy has provided further insight into the mechanism of action of ribavirin.[45] This study tested the hypothesis that ribavirin acts by causing lethal mutagenesis to the virus, and the traditional model was, therefore, extended to incorporate a term accounting for these effects. The results fit well into this revised model. Moreover, findings from this study indicated that ribavirin enhances the second-phase viral decline, but that its enhancement was substantial only when IFN effectiveness was low. Figure 4 shows theoretic decay profiles for high and low IFN effectiveness. In patients with high IFN effectiveness, the second-phase viral decline is not significantly affected by increasing the effectiveness of ribavirin. In contrast, when IFN effectiveness is low, increasing ribavirin effectiveness has a greater impact on the second-phase viral decline. The authors of this study also theorized on what ETR and SVR rates should be, based on the addition of ribavirin. In general, predictions from this model were in agreement with the response rates from previous clinical trials."
From:
<A HREF="http://www.medscape.com/viewarticle/543530?src=mp/">Viral Kinetics in the Treatment of Chronic Hepatitis C</A>
"Kinetic parameters were also studied when ribavirin was used in conjunction with pegylated IFN.[44] In this study, it was hypothesized that ribavirin served as an immune modulator. To account for this effect, the basic kinetic model also included an additional term called an inflation factor that had an impact on the rate of loss of infected cells after an initial delay. The study confirmed the observation that ribavirin had little impact on the first-phase viral decline, but increased the second-phase viral decline, when IFN effectiveness was low. A third phase was also noted, which may represent an enhanced loss in the rate of infected cells.
A recent study that modelled the impact of ribavirin on IFN therapy has provided further insight into the mechanism of action of ribavirin.[45] This study tested the hypothesis that ribavirin acts by causing lethal mutagenesis to the virus, and the traditional model was, therefore, extended to incorporate a term accounting for these effects. The results fit well into this revised model. Moreover, findings from this study indicated that ribavirin enhances the second-phase viral decline, but that its enhancement was substantial only when IFN effectiveness was low. Figure 4 shows theoretic decay profiles for high and low IFN effectiveness. In patients with high IFN effectiveness, the second-phase viral decline is not significantly affected by increasing the effectiveness of ribavirin. In contrast, when IFN effectiveness is low, increasing ribavirin effectiveness has a greater impact on the second-phase viral decline. The authors of this study also theorized on what ETR and SVR rates should be, based on the addition of ribavirin. In general, predictions from this model were in agreement with the response rates from previous clinical trials."
Here's another,
http://clinicaloptions.com/layouts/CCO.Web.aspx?path=/CCO/hepatitis/annual+updates/2006+annual+update/modules/davis/pages/page+1&layout={89AD1AF7-1174-436A-B482-E964EA6098A0}
Which opens by saying:
"The current standard of care for the treatment of chronic hepatitis C virus (HCV) infection is the combination of peginterferon and ribavirin,[1,2] despite the fact that the precise mechanisms of action for these drugs, when used to combat hepatitis C, are still unknown. Nonetheless, eradication of virus has not only been proven possible, but is also associated with significant improvement in histology and prognosis and constitutes the present goal of anti-HCV therapy.
Although interferon-based combination therapy is quite effective for qualified hepatitis C patients,[3] treatment is lengthy (up to 1 year
It seemd as though you were struggling with conceptualizing the theories on the mechanism of ribavirin.
"concentration of riba does play a very significant role in chances of UND by allowing IFN to killing virus and preventing it from replicating during the onset of tx."
"concentration of riba does play a very significant role in chances of UND by allowing IFN to killing virus and preventing it from replicating during the onset of tx."
That depends. Both papers we've cited make it clear that Riba prevent viral replication.
But as the paper I cited explains exactly how it achieves this is not known, or understood.
Even the quote you providing cites that it is hypothesized "that ribavirin acts by causing lethal mutagenesis to the virus", which appears to fit their traditional model. However, that is still a hypothesis which has yet to be proven out.
What my tx has proven to me is that it most definitely has a significant effect upon viral reduction and depends largely upon the dosage used as to how effective it is, which would provide some support to weight-based dosing of ribavirin.
But as the paper I cited explains exactly how it achieves this is not known, or understood.
Even the quote you providing cites that it is hypothesized "that ribavirin acts by causing lethal mutagenesis to the virus", which appears to fit their traditional model. However, that is still a hypothesis which has yet to be proven out.
What my tx has proven to me is that it most definitely has a significant effect upon viral reduction and depends largely upon the dosage used as to how effective it is, which would provide some support to weight-based dosing of ribavirin.
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