Aa
Two new articles: Extrahepatic Manifestations Part 2,
Here are two additional articles worth reading for those who may be interested in the topics. The first is a Part 2 follow up to the article that I posted last week on Extrahepatic Manifestations of HCV:
http://www.natap.org/2006/HCV/042106_01.htm
The second article discusses the current state-of-art regarding Tailoring HCV Therapy, for optimal response...but most of the discussion relates to the use of RVR (4 week PCR status) for making decisions about therapy.
http://www.natap.org/2006/HCV/042106_02.htm
Also please use this thread to discuss any ongoing questions from the past week regarding the above issues, late relapse, persistent virus, extended treatment, or any other 'hot' topic of discussion from the past week.
I hope all our members are doing well, and keeping in touch. If you have a question or a concern, you will find diverse, well- thought-out responses here. It is up to you to absorb them all, and come up with your own ideas and strategies. Hopefully a great deal of current, relevant information will be made available by our long term forum veterans, that will assist in making better decisions, or just asking your doctor the right questions.
DoubleDose
http://www.natap.org/2006/HCV/042106_01.htm
The second article discusses the current state-of-art regarding Tailoring HCV Therapy, for optimal response...but most of the discussion relates to the use of RVR (4 week PCR status) for making decisions about therapy.
http://www.natap.org/2006/HCV/042106_02.htm
Also please use this thread to discuss any ongoing questions from the past week regarding the above issues, late relapse, persistent virus, extended treatment, or any other 'hot' topic of discussion from the past week.
I hope all our members are doing well, and keeping in touch. If you have a question or a concern, you will find diverse, well- thought-out responses here. It is up to you to absorb them all, and come up with your own ideas and strategies. Hopefully a great deal of current, relevant information will be made available by our long term forum veterans, that will assist in making better decisions, or just asking your doctor the right questions.
DoubleDose
Couldn't agree more. And until occult, persistent, and low level resovoirs re-emerge as "relape" in more than a statistical rarity of patients, any speculation about real-world clinical signficance (yet to be shown) is simply that -- speculation. I think this should be made clear when we post these types of studies -- and make these speculations -- because they can sound very scary to those new to the subject.
That said, hopefully this type of research will go on and start exploring the clinical signifance (if any) of these below-the-radar replicating viruses -- assuming that are conclusively proven to exist.
After all, we all want as much of a "cure" as medically possible, but I do feel it counter-productive -- at least for myself -- to strive or dwell on anything other than the established goal which has already been shown to be not only durable but to halt and even regress fibrosis in many cases. And that's plain ole SVR.
-- Jim
That said, hopefully this type of research will go on and start exploring the clinical signifance (if any) of these below-the-radar replicating viruses -- assuming that are conclusively proven to exist.
After all, we all want as much of a "cure" as medically possible, but I do feel it counter-productive -- at least for myself -- to strive or dwell on anything other than the established goal which has already been shown to be not only durable but to halt and even regress fibrosis in many cases. And that's plain ole SVR.
-- Jim
Couldn't find T cell article that Jim mentioned although there is a lot written on the subject. Did find a couple of other things:
Article by Daniel Raymond from HARM project about new therapies. Concise and up to date:
http://www.poz.com/articles/451_2792.shtml
Also some interesting comments from Raymond from Liver Meeting (scroll down to see his comments) - couple of years old but his comments about virus remaining in the blood are on topic for what people have been talking about here. Take a look at the comment by one of the other doctors who says that she will stop using the "C Word" (cure).
http://hepcproject.typepad.com/hep_c_project/2004/11/update_from_the.html
Article by Daniel Raymond from HARM project about new therapies. Concise and up to date:
http://www.poz.com/articles/451_2792.shtml
Also some interesting comments from Raymond from Liver Meeting (scroll down to see his comments) - couple of years old but his comments about virus remaining in the blood are on topic for what people have been talking about here. Take a look at the comment by one of the other doctors who says that she will stop using the "C Word" (cure).
http://hepcproject.typepad.com/hep_c_project/2004/11/update_from_the.html
it's interesting that that <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=16107964%5Bpmid%5D">patient</a> exhibited a rare pattern that, unless my memory is playing tricks on me, has also been reported a couple of times on this board : quick post-tx relapse followed by later disappearance of the virus.
Here's a summary from the closing paragraph of that paper, it's interesting that the authors are cautious about whether the yo-yo behavior in viral suppression was due to her hypogammaglobulinemia or to the immuno-suppressants.
"<em>Our patient experienced an immediate relapse after 5 months of IFN therapy, which was followed by viral clearance for 8.5 years. The very-delayed relapse of infection after >8 years may have resulted from transient immunosuppression due to repeated corticosteroid use. However, other factors, including abnormal immunity and cytokine signaling associated with hypogammaglobulinemia, could also have effected this relapse pattern [14]. That the phenomenon did not represent reinfection was proved by the fact that only a single amino acid difference in the NS5A region was found over the 8.5-year period. We interpret the minimal shift in quasispecies diversity and the repeatedly negative serum HCV RNA PCR assays to represent a low level of viral replication during this long quiescent period. Although considered to be a sustained viral responder, our patient continued to have a reservoir of low-replicating virus that was held in check but not eradicated by her immune system until the corticosteroid-induced immune suppression led to the relapse. Recent studies in immunocompetent patients support the presence of such a reservoir [15]. An HCV reservoir that requires continued innate or T cell immune surveillance to prevent disease activity even years after the infection appeared to have resolved may exist in at least some sustained viral responders. </em>"
putting this together with pham/radkowski/pardo seems to point to the conclusion that though "reservoirs" may not be all rare, breakdowns in the durability of SVR are. Durability is the real cure.
Here's a summary from the closing paragraph of that paper, it's interesting that the authors are cautious about whether the yo-yo behavior in viral suppression was due to her hypogammaglobulinemia or to the immuno-suppressants.
"<em>Our patient experienced an immediate relapse after 5 months of IFN therapy, which was followed by viral clearance for 8.5 years. The very-delayed relapse of infection after >8 years may have resulted from transient immunosuppression due to repeated corticosteroid use. However, other factors, including abnormal immunity and cytokine signaling associated with hypogammaglobulinemia, could also have effected this relapse pattern [14]. That the phenomenon did not represent reinfection was proved by the fact that only a single amino acid difference in the NS5A region was found over the 8.5-year period. We interpret the minimal shift in quasispecies diversity and the repeatedly negative serum HCV RNA PCR assays to represent a low level of viral replication during this long quiescent period. Although considered to be a sustained viral responder, our patient continued to have a reservoir of low-replicating virus that was held in check but not eradicated by her immune system until the corticosteroid-induced immune suppression led to the relapse. Recent studies in immunocompetent patients support the presence of such a reservoir [15]. An HCV reservoir that requires continued innate or T cell immune surveillance to prevent disease activity even years after the infection appeared to have resolved may exist in at least some sustained viral responders. </em>"
putting this together with pham/radkowski/pardo seems to point to the conclusion that though "reservoirs" may not be all rare, breakdowns in the durability of SVR are. Durability is the real cure.
I agree that it seems different people's immune system have handled the eradication of HCV differently. It does seem as if some clear it completely, no compartmentalization or hiding, and others are keeping it at bay. The latter is almost confirmed by the case of the woman who "relapsed" after 8 yrs due to steroid therapy. In my opinion she does not seem to be SVR, given the fact that she tested negative by whatever PCR sensitivity was used, tested positive after steroidal therapy and returned to negative status after the therapy ended. It looks as if her system is very efficient in keeping a very low viral load. \
As Jm mentioned, almost no relapses occur after a yr SVR, if any. whether the person treats with steroids or binge drinks, which I am sure some must have done post hcv tx, has not brought a positive PCR. Are these immune systems even more powerful than the mentioned lady, or is the virus truly gone, permanently deactivated?
There is so much speculation as to what a few rna strands might mean and still no confirmation. Just because hcv and varicella zoster are both viruses, it does not mean they act the same. SOme viruses do not have latency periods, the cold virus for example, and do not resurface later on when we are immunosuppresed. There are so many out there with the SVR label, and some must have undergone steroidal therapy or other tx at some point with no relapse or temporary positive PCR.
and the speculation lives on...
As Jm mentioned, almost no relapses occur after a yr SVR, if any. whether the person treats with steroids or binge drinks, which I am sure some must have done post hcv tx, has not brought a positive PCR. Are these immune systems even more powerful than the mentioned lady, or is the virus truly gone, permanently deactivated?
There is so much speculation as to what a few rna strands might mean and still no confirmation. Just because hcv and varicella zoster are both viruses, it does not mean they act the same. SOme viruses do not have latency periods, the cold virus for example, and do not resurface later on when we are immunosuppresed. There are so many out there with the SVR label, and some must have undergone steroidal therapy or other tx at some point with no relapse or temporary positive PCR.
and the speculation lives on...
landfill: sorry, I don't know yet - should find out within a couple of weeks
dd: there is some relief in moving another symptom from the suspect, self-reported, category to join the symptoms with a known mechanism. However, the fact that it took this long to identify something as universally reported as brain-fog suggests it might be a long time indeed before the extra-hepatic effects of low-level infection are understood...(btw here's another interesting extra-hepatic article on hcv in <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16618405&query_hl=2&itool=pubmed_docsum">lymph cells</a> that suggests replication outside the liver may play a major role in overall viral count. I wonder whether this helps make sense of the "viral count is uncorrelated with liver damage" puzzle).
jim/goofy - thanks, I'll keep looking. What I like about this test is that it seems better correlated with the positive aspects of SVR. There's no real challenge to either the durability of SVR or its beneficial effect on long term cirrhosis/hcc outlook. If "cure" becomes redefined to mean training the immune response to keep viral replication in the liver in check rather than to mean viral eradication, all this lingering ambivalence about using the term would vanish.
tn: thanks for the occult hepB links. I think extrapolating the occult HBV finding to HCV is a stretch. Chronic HBV is a much nastier bug (worse hcc rates, harder to treat). The studies that have reported post-SVR HCV find it in nearly everyone (eg the Pardo 5/5). This implies the residual virus can't have much of an effect on liver mortality or all those long-term fibrosis/hcc follow ups wouldn't look so rosy.
dd: there is some relief in moving another symptom from the suspect, self-reported, category to join the symptoms with a known mechanism. However, the fact that it took this long to identify something as universally reported as brain-fog suggests it might be a long time indeed before the extra-hepatic effects of low-level infection are understood...(btw here's another interesting extra-hepatic article on hcv in <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16618405&query_hl=2&itool=pubmed_docsum">lymph cells</a> that suggests replication outside the liver may play a major role in overall viral count. I wonder whether this helps make sense of the "viral count is uncorrelated with liver damage" puzzle).
jim/goofy - thanks, I'll keep looking. What I like about this test is that it seems better correlated with the positive aspects of SVR. There's no real challenge to either the durability of SVR or its beneficial effect on long term cirrhosis/hcc outlook. If "cure" becomes redefined to mean training the immune response to keep viral replication in the liver in check rather than to mean viral eradication, all this lingering ambivalence about using the term would vanish.
tn: thanks for the occult hepB links. I think extrapolating the occult HBV finding to HCV is a stretch. Chronic HBV is a much nastier bug (worse hcc rates, harder to treat). The studies that have reported post-SVR HCV find it in nearly everyone (eg the Pardo 5/5). This implies the residual virus can't have much of an effect on liver mortality or all those long-term fibrosis/hcc follow ups wouldn't look so rosy.
Very well put. Durability is indeed the name of the game, and whether the low level, persistent stuff exists or not, it may be a moot point after all. Let's hope so!!!
DD
DD
Willing: ... I'd be curious to read the paper about the immune-based test if you find it...
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There is no paper I'm aware of on the test my doctor mentioned. When I brought up the subject again at my last visit (because of course I wanted the test :) ) he inferred things were still in the research/theoretical stage.
To put things in context, this is how the topic came about, as best as I remember it...
Sometime around week 44 of treatment, I asked him what my chances of SVR were. He seemed in a reflective mood that day, so instead of giving me stats as usual, he responded by saying, "I wish we knew".
Then he went on to say that the only way to really know is by testing the quality of the t-cell response. In other words, has the patient on tx showing non-detectible, achieved a standalone, i.e. durable t-cell response, or has the patient achieved a transitory tx-induced false t-cell response that will fall flat when the treatment drugs are removed from the equation.
In any event, I did pull up an article a few months ago that echoed his thoughts, at least in reference to infectious diseases in general if I remember correctly. The link probably was posted around the time I first brought this topic up and maybe someone can have better luck finding it in the archives than I.
It would be great if I could sit down with him for 30 minutes on this topic to learn more, but I frankly don't have that kind of relationship and I have only so much time per visit to address all my treatment concerns.
However, if anyone wants you do google "t cell response hepatitis c" or "t cell response infectious diseases" you should come up with a slew of relevant articles and maybe one that will address drug induced t-cell response versus a response that will last beyond.
-- Jim
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There is no paper I'm aware of on the test my doctor mentioned. When I brought up the subject again at my last visit (because of course I wanted the test :) ) he inferred things were still in the research/theoretical stage.
To put things in context, this is how the topic came about, as best as I remember it...
Sometime around week 44 of treatment, I asked him what my chances of SVR were. He seemed in a reflective mood that day, so instead of giving me stats as usual, he responded by saying, "I wish we knew".
Then he went on to say that the only way to really know is by testing the quality of the t-cell response. In other words, has the patient on tx showing non-detectible, achieved a standalone, i.e. durable t-cell response, or has the patient achieved a transitory tx-induced false t-cell response that will fall flat when the treatment drugs are removed from the equation.
In any event, I did pull up an article a few months ago that echoed his thoughts, at least in reference to infectious diseases in general if I remember correctly. The link probably was posted around the time I first brought this topic up and maybe someone can have better luck finding it in the archives than I.
It would be great if I could sit down with him for 30 minutes on this topic to learn more, but I frankly don't have that kind of relationship and I have only so much time per visit to address all my treatment concerns.
However, if anyone wants you do google "t cell response hepatitis c" or "t cell response infectious diseases" you should come up with a slew of relevant articles and maybe one that will address drug induced t-cell response versus a response that will last beyond.
-- Jim
Goofy says:It's possible some SVRs have cleared the virus completely before stopping therapy, while others leave the mopping up, or long term suppression to be handled by their own immune systems, unaided by interferon.
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Just to keep the discussion going...an alternate theory is that it can take up to six months for any potent "hiding" virus to re-emerge. But after that point, the odds of that happening diminish greatly and at the 1 year post tx mark the durability of SVR approaches 100%. Another thought I had is the "switch" theory. Being that in SVRs at some point the immune system throws a switch that in almost all cases is one-way. Once the switch is thrown, the immune system is now strong enough to keep any residual virus from doing any harm. The former is consistent with what a second heapatologist told me. The latter, just some late night thoughts.
-- Jim
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Just to keep the discussion going...an alternate theory is that it can take up to six months for any potent "hiding" virus to re-emerge. But after that point, the odds of that happening diminish greatly and at the 1 year post tx mark the durability of SVR approaches 100%. Another thought I had is the "switch" theory. Being that in SVRs at some point the immune system throws a switch that in almost all cases is one-way. Once the switch is thrown, the immune system is now strong enough to keep any residual virus from doing any harm. The former is consistent with what a second heapatologist told me. The latter, just some late night thoughts.
-- Jim
Miss,
No offense taken, I was just kidding you. :)
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Goofy says: I have no idea what the reality is, I just posted the statement from my Doc to stimulate some discussion.
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Ditto. And I'm also erring on the side of caution during these next few months for exactly the same reason.
No offense taken, I was just kidding you. :)
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Goofy says: I have no idea what the reality is, I just posted the statement from my Doc to stimulate some discussion.
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Ditto. And I'm also erring on the side of caution during these next few months for exactly the same reason.
Thanks for the discussion, interesting to get the points of view. Just wanted to point out that both positions could be valid. It's possible some SVRs have cleared the virus completely before stopping therapy, while others leave the mopping up, or long term suppression to be handled by their own immune systems, unaided by interferon.
Jim, as for the infrequency of late term relapses, my guess would be that once the naked immune system has proven itself for 6-12 months, it is fully established against the virus. I have no idea what the reality is, I just posted the statement from my Doc to stimulate some discussion.
For me, the take away is to try to keep the ol' immune system running on all cylinders for at least the next few months. Now I need to figure out what that means and how to do it. I think the Mayans used to sacrafice goats, or was it virgins? Hmmmm, more research.....how about I volunteer for some hands on study with the virgins - someone else can take the goats.
Anyone know where virgin cashmere comes from? Yup. Ugly goats.
Jim, as for the infrequency of late term relapses, my guess would be that once the naked immune system has proven itself for 6-12 months, it is fully established against the virus. I have no idea what the reality is, I just posted the statement from my Doc to stimulate some discussion.
For me, the take away is to try to keep the ol' immune system running on all cylinders for at least the next few months. Now I need to figure out what that means and how to do it. I think the Mayans used to sacrafice goats, or was it virgins? Hmmmm, more research.....how about I volunteer for some hands on study with the virgins - someone else can take the goats.
Anyone know where virgin cashmere comes from? Yup. Ugly goats.
Willing
Thanks for the article. Goes to show that doctors will only believe what patients tell them, even if in large numbers, only when there is scientific proof. In other words, why bother to treat the imaginings of patients.....until...oops! by golly I guess this stuff really exists. Several doctors I have spoken with are fond of stating that HCV patients develop many of their symptoms after they find out they have HCV. That sure is a slap in the face!
Jim,
I really think that the articles cited ARE saying that replicative virus is being found, many years after SVR, in the great majority of patients studied.
Now, please do not go bananas on me here as I resurface one of my old 'what if' theories, but here it is:
What if it takes a MAJOR event to spark a real HCV infection in most people. Like a transfusion or intravenous drug apparatus, laden with blood borne HCV???? What if some people could carry a dormant version of the virus (similar to the 'persistent infection after SVR' crowd),.. without ever lapsing into true blood/liver infection. Maybe the immune system holds the virus in low threshold 'check' in millions of people, and the only ones that really get the illness, are the ones whose blood is flooded with the virus....OR, those who have their immune systems 'shut down' due to disease, or drug therapy.
Could there be many people with a latent HCV virus dormant in organs other than the blood, whose immune system just contains the virus, and prevents true infection????
This is one thought I have had.
Again, just pure logical projection....conjecture....
DoubleDose
Thanks for the article. Goes to show that doctors will only believe what patients tell them, even if in large numbers, only when there is scientific proof. In other words, why bother to treat the imaginings of patients.....until...oops! by golly I guess this stuff really exists. Several doctors I have spoken with are fond of stating that HCV patients develop many of their symptoms after they find out they have HCV. That sure is a slap in the face!
Jim,
I really think that the articles cited ARE saying that replicative virus is being found, many years after SVR, in the great majority of patients studied.
Now, please do not go bananas on me here as I resurface one of my old 'what if' theories, but here it is:
What if it takes a MAJOR event to spark a real HCV infection in most people. Like a transfusion or intravenous drug apparatus, laden with blood borne HCV???? What if some people could carry a dormant version of the virus (similar to the 'persistent infection after SVR' crowd),.. without ever lapsing into true blood/liver infection. Maybe the immune system holds the virus in low threshold 'check' in millions of people, and the only ones that really get the illness, are the ones whose blood is flooded with the virus....OR, those who have their immune systems 'shut down' due to disease, or drug therapy.
Could there be many people with a latent HCV virus dormant in organs other than the blood, whose immune system just contains the virus, and prevents true infection????
This is one thought I have had.
Again, just pure logical projection....conjecture....
DoubleDose
Goofy said: I think this is pretty interesting. I believe most of us perceive complete erradication of the virus as the end-point of tx, but I think (my doctor's) take is that tx is actually more training the imune system as opposed to erradicating the virus.
I think this position is reasonably aligned with the blood test Jim described that measured presence of a particular T cell at end-of-treatment in order to predict relapse.
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First, I also find this topic of great interest. Second, it appears that both of our (big hitter) hepatologists have different views on the role of the immune system post treatment. Goofy states his doc's opinion above. My doc feels the immune system is critical to killing the virus, but once dead, it doesn't come back regardless of the immune system because there isn't any virus to come back. Goof -- it probably would be of great interest to all of us if you could wrangle a study or two from your doctor, should one exist.
Regarding the T-cell test I mentioned a month of so ago. My understanding is that it's still experimental. But the concept, as explained by my doc, is that this particular test theoretically would show whether the immune response during treatment was simply a transitory treatment induced response or a profound response. If the latter, we would have SVR. If the former, probably relapse.
So Goof -- are you and your doc saying I should wait awhile before popping the lid on that Amstel Light?
-- Jim
I think this position is reasonably aligned with the blood test Jim described that measured presence of a particular T cell at end-of-treatment in order to predict relapse.
-----------------------------------------------------------------
First, I also find this topic of great interest. Second, it appears that both of our (big hitter) hepatologists have different views on the role of the immune system post treatment. Goofy states his doc's opinion above. My doc feels the immune system is critical to killing the virus, but once dead, it doesn't come back regardless of the immune system because there isn't any virus to come back. Goof -- it probably would be of great interest to all of us if you could wrangle a study or two from your doctor, should one exist.
Regarding the T-cell test I mentioned a month of so ago. My understanding is that it's still experimental. But the concept, as explained by my doc, is that this particular test theoretically would show whether the immune response during treatment was simply a transitory treatment induced response or a profound response. If the latter, we would have SVR. If the former, probably relapse.
So Goof -- are you and your doc saying I should wait awhile before popping the lid on that Amstel Light?
-- Jim
Jim asked GoofyDad:
"First, I also find this topic of great interest. Second, it appears that both of our (big hitter) hepatologists have different views on the role of the immune system post treatment. Goofy states his doc's opinion above. My doc feels the immune system is critical to killing the virus, but once dead, it doesn't come back regardless of the immune system because there isn't any virus to come back. Goof -- it probably would be of great interest to all of us if you could wrangle a study or two from your doctor, should one exist. "
I will address this question briefly by citing two related articles (there are other similar studies by other researchers), that provide an opinion of SVR that is closer to Goof's doctor. Not that I am in total agreement, its just that there are research studies backing up both points of view, with very specific data and testing outcomes. They are as below:
http://www.hivandhepatitis.com/hep_c/news/2005/021805_b.html
http://www.hivandhepatitis.com/hep_c/news/2005/010305_a.html
These are the types of confusing and concerning studies that are causing some HCV doctors to become less 'cure' focused, and more 'suppression' oriented. This is a major 'grey' area in HCV research!
Also, there is the recent article about the person who relapsed after 8 years of SVR, after undergoing a course of immuno-suppressive therapy. This plays right into the implications made by the above articles.
DoubleDose
"First, I also find this topic of great interest. Second, it appears that both of our (big hitter) hepatologists have different views on the role of the immune system post treatment. Goofy states his doc's opinion above. My doc feels the immune system is critical to killing the virus, but once dead, it doesn't come back regardless of the immune system because there isn't any virus to come back. Goof -- it probably would be of great interest to all of us if you could wrangle a study or two from your doctor, should one exist. "
I will address this question briefly by citing two related articles (there are other similar studies by other researchers), that provide an opinion of SVR that is closer to Goof's doctor. Not that I am in total agreement, its just that there are research studies backing up both points of view, with very specific data and testing outcomes. They are as below:
http://www.hivandhepatitis.com/hep_c/news/2005/021805_b.html
http://www.hivandhepatitis.com/hep_c/news/2005/010305_a.html
These are the types of confusing and concerning studies that are causing some HCV doctors to become less 'cure' focused, and more 'suppression' oriented. This is a major 'grey' area in HCV research!
Also, there is the recent article about the person who relapsed after 8 years of SVR, after undergoing a course of immuno-suppressive therapy. This plays right into the implications made by the above articles.
DoubleDose
DD,
I'll get to the articles later, but one question. If it's reall up to the immune system to suppress the virus after SVR, then how come there is almost a statistically insignificant number of relapses after say the post tx 1 year mark? So, assuming there is some role for the immune system to play -- if it doesn't impact us at all as patients, then where is the relevancy?
Regarding one of the articles you posted, this one quote really killed me:
"Perhaps the biggest downside of RVR is the potential impact of increasing the complexity of the treatment algorithm for chronic hepatitis C. Utilization of RVR will entail stratifying patients to different regimens of treatment based on baseline genotype and levels of virus before initiation of therapy. "
In other words, the biggest side of using RVR is TOO MUCH WORK FOR THE DOCTOR, including too much labor and actually requiring the doctor to do some homework other than reading drug company labeling. Gosh. Horrible. What a nightmare for them.
This is why we as patients have to demand better and more individualized treatment using whatever is out there. Fortunately, there are a number of doctors who are already doing this.
-- Jim
I'll get to the articles later, but one question. If it's reall up to the immune system to suppress the virus after SVR, then how come there is almost a statistically insignificant number of relapses after say the post tx 1 year mark? So, assuming there is some role for the immune system to play -- if it doesn't impact us at all as patients, then where is the relevancy?
Regarding one of the articles you posted, this one quote really killed me:
"Perhaps the biggest downside of RVR is the potential impact of increasing the complexity of the treatment algorithm for chronic hepatitis C. Utilization of RVR will entail stratifying patients to different regimens of treatment based on baseline genotype and levels of virus before initiation of therapy. "
In other words, the biggest side of using RVR is TOO MUCH WORK FOR THE DOCTOR, including too much labor and actually requiring the doctor to do some homework other than reading drug company labeling. Gosh. Horrible. What a nightmare for them.
This is why we as patients have to demand better and more individualized treatment using whatever is out there. Fortunately, there are a number of doctors who are already doing this.
-- Jim
OK. I read the two articles but I don't see either of them supporting or not supporting the position Goofy's doctor takes. They're more about viral persistence after SVR with the suggestion that if the virus persists it may reactivate. My hepatologists reaction to viral persistence is that these are incomplete, often non-replicating viruses that have not yet shown any clinical significance in terms of relapse. The relapse stats do seem to be the smoking gun here and bear him out. Again, why aren't we seeing more relapses after 1 year in SVR's -- and I'm not talking about very isolated cases. After all, it's not like our treatment population is the youngest of young or the healthiest of healthy. Just some thoughts.
-- Jim
-- Jim
jim: you might ask your Dr. what his take is on the detection of negative strand RNA in various cell types (lymphocytes,macrophages, PBMCS) in the Pham/Radkowski studies (cites in earlier threads). To my mind that's pretty much a smoking gun - negative strand is only produced during viral replication. Also, I'd be curious to read the paper about the immune-based test if you find it. Looking at tx as giving your immune response another shot at the job it blew the first time around rings true to me as well. (<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16262527&query_hl=6&itool=pubmed_DocSum">eg</a>.
DD - thanks for the links. Here's more detail about verfication (finally!) of a common extra-hepatic side effect many of us have been aware of for years, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16251812&query_hl=1&itool=pubmed_docsum">brain-fog</a>.
DD - thanks for the links. Here's more detail about verfication (finally!) of a common extra-hepatic side effect many of us have been aware of for years, <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16251812&query_hl=1&itool=pubmed_docsum">brain-fog</a>.
Sorry if I mislead on the TMA. It did begin with "T." I just can't keep up with Jim - moving on to T cell measurements - what's next, connecting the dots on the riba rash to reveal a hidden yes or no on SVR?
This may be a good time to ask how many of us actually have herpes simples/shingles. I am not talking about sexual herpes here. Shingles is something that can stay hidden for years and surface during an acute illness or just finally show up one day. The same thing with herpes I think. Both HCV and herpes simplex are a virus. I believe that we have so much more to learn about viruses in general that we have just begun to touch the surface.
Any comments on the above? I have not seen anything written about the two together. Thanks for all the links to the info. I agree we need to know more than our docs about a lot of things.
missmiss
Any comments on the above? I have not seen anything written about the two together. Thanks for all the links to the info. I agree we need to know more than our docs about a lot of things.
missmiss
miss says This may be a good time to ask how many of us actually have herpes simples/shingles.
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Not sure why I was singled for this question LOL but other than getting a cold sore on my lips every four or five years, haven't had any problems. My understanding is that cold sores are very common in the general population so I never associated it with Hep c. Actually, I didn't associated ANYTHING with Hep C (except some occasional fatigue) until I joined this discussion group. LOL.
-- Jim
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Not sure why I was singled for this question LOL but other than getting a cold sore on my lips every four or five years, haven't had any problems. My understanding is that cold sores are very common in the general population so I never associated it with Hep c. Actually, I didn't associated ANYTHING with Hep C (except some occasional fatigue) until I joined this discussion group. LOL.
-- Jim
I am so sorry. Please don't take offense. I picked you because I could remember your handle from your posts above AND you do seem to be very knowledgable. My memory of members names, stats, etc is extremely limited. I mean noone any offense.
Sorry! :-)
miss
Sorry! :-)
miss
I should probably add at this point that I haven't taken a position either way on this and personally agree with DD's assertion that we're in a very grey (and theoretical) are here with no studies I know of that show clinical significance. By adding a couple of my doctor's opinions, I hope the conversation here will be rounded out more. I also have my own questions, such as why don't we see more than a rare relapse after 1 year post tx, if the virus does persist in any meaningful way post treatment. More questions than answers on this particular topic for me.
-- Jim
-- Jim
DD says:I really think that the articles cited ARE saying that replicative virus is being found, many years after SVR, in the great majority of patients studied.
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I think they are SUGGESTING some form of viral replication is taking place but I don't pretend to know the intricacies between the different forms of virus they are examining. But again, what is the clinical significance? In case I've read the studies wrong, none of them go there. And as I stated to Willing, I'm not taking a position one way or another, just adding to the discussion which probably has no right answer at this current point in time. Hope this finds you well.
-- Jim
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I think they are SUGGESTING some form of viral replication is taking place but I don't pretend to know the intricacies between the different forms of virus they are examining. But again, what is the clinical significance? In case I've read the studies wrong, none of them go there. And as I stated to Willing, I'm not taking a position one way or another, just adding to the discussion which probably has no right answer at this current point in time. Hope this finds you well.
-- Jim
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