Aa
'hepatitisresearcher' re: more on occult
Thanks for taking the time to answer my questions. I'll post one here that 'willing' had asked below, as well as a related follow-up (or two) that I have.
(from 'willing'):
- "<i>It would be interesting to hear your comments on the validity of the data in <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16628675&query_hl=6&itool=pubmed_docsum">Giannini'06</a>...</i>"
(from me):
- it appears that in the above linked paper (Giannini), a direct associative link is drawn between occult and cryo in SOI patients. <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17051492&query_hl=9&itool=pubmed_DocSum">Castillo '06</a> and <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16611276&query_hl=2&itool=pubmed_docsum">Pardo '06</a> both talk of ongoing necroinflammation in occult patients, with Pardo's conclusion being: "<i>The biochemical, virological and histological response to therapy achieved in patients with occult hepatitis C virus infection demonstrates the <b>pathologic effects of occult hepatitis C virus</b></i>". <a href="http://www.mlo-online.com/articles/0206/0206clinical_issues.pdf">In Pham '06</a> he states "<i>Although these
patients generally exhibit histologically apparent improvement
after IFN-alpha/Ribavirin therapy, including partial regression
of fibrosis, liver biopsies from many of them show evidence
of persistent minimal inflammation or even of active chronic
hepatitis.3,5</i>"
(from 'willing'):
- "<i>It would be interesting to hear your comments on the validity of the data in <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16628675&query_hl=6&itool=pubmed_docsum">Giannini'06</a>...</i>"
(from me):
- it appears that in the above linked paper (Giannini), a direct associative link is drawn between occult and cryo in SOI patients. <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17051492&query_hl=9&itool=pubmed_DocSum">Castillo '06</a> and <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16611276&query_hl=2&itool=pubmed_docsum">Pardo '06</a> both talk of ongoing necroinflammation in occult patients, with Pardo's conclusion being: "<i>The biochemical, virological and histological response to therapy achieved in patients with occult hepatitis C virus infection demonstrates the <b>pathologic effects of occult hepatitis C virus</b></i>". <a href="http://www.mlo-online.com/articles/0206/0206clinical_issues.pdf">In Pham '06</a> he states "<i>Although these
patients generally exhibit histologically apparent improvement
after IFN-alpha/Ribavirin therapy, including partial regression
of fibrosis, liver biopsies from many of them show evidence
of persistent minimal inflammation or even of active chronic
hepatitis.3,5</i>"
What does the word " occult " mean? I have seen this word numerous times and am just wondering what it is and means?
I thought I'd bring up my last post in the "parent" thread to this one for your thoughts:
------------------------------------------------------
HR: "...Again what mostly matters here is the stability of the SVR and that seems to be surprisingly good...more surprising now in the light of the new findings..."
-----------------------------------
For me, this seems the crux of the matter to date. Some researchers are finding "stuff" in compartments other than serum in SVRs. This stuff, which HR has characterized in part as residual mutations of a remant trash virus (MTV :)), may indeed not turn out to be harmful to its host SVR. In fact, there are many types of virus -- such as Epstein Barr -- commonly found in the population that pose no real threat when kept in check by the immune system.
As HR suggests, the eventual way to deal with all these MTV residuals may not be a new drug, but in fact it may be a simple common sense approach to living that fosters a healthy immune systems --
such as eating well, keeping to a proper weight, exercise, etc.
With SVR durable, and the other "stuff" safely locked behind the serum barrier wall with no proven harm, we SVRs should be put at ease. Further research may or may not contradict this, but isn't that always the case.
Hopefully, I haven't mischaracterized HR's statments, and surely he will correct me if I did. My "spin" if you want to call it that, may be more positive than some might express, more negative than others. This should not be surprising when we're dealing with topics still more in the research stage than in the clinical.
All the best,
-- Jim
------------------------------------------------------
HR: "...Again what mostly matters here is the stability of the SVR and that seems to be surprisingly good...more surprising now in the light of the new findings..."
-----------------------------------
For me, this seems the crux of the matter to date. Some researchers are finding "stuff" in compartments other than serum in SVRs. This stuff, which HR has characterized in part as residual mutations of a remant trash virus (MTV :)), may indeed not turn out to be harmful to its host SVR. In fact, there are many types of virus -- such as Epstein Barr -- commonly found in the population that pose no real threat when kept in check by the immune system.
As HR suggests, the eventual way to deal with all these MTV residuals may not be a new drug, but in fact it may be a simple common sense approach to living that fosters a healthy immune systems --
such as eating well, keeping to a proper weight, exercise, etc.
With SVR durable, and the other "stuff" safely locked behind the serum barrier wall with no proven harm, we SVRs should be put at ease. Further research may or may not contradict this, but isn't that always the case.
Hopefully, I haven't mischaracterized HR's statments, and surely he will correct me if I did. My "spin" if you want to call it that, may be more positive than some might express, more negative than others. This should not be surprising when we're dealing with topics still more in the research stage than in the clinical.
All the best,
-- Jim
Must you inject your "every-expert-agrees-me-and-my-two-unerring-hepatologists-as-long-as-I-can-get-the-last-post-in" routine into this thread, too???
Give it a break, stop the incessant bloviating and let the man answer (or not) the questions posed to him at the top of the thread - and let it stand at that.
If you've got some questions to pose, fire up your own thread and have a nice back-and-forth.
TnHepGuy
Give it a break, stop the incessant bloviating and let the man answer (or not) the questions posed to him at the top of the thread - and let it stand at that.
If you've got some questions to pose, fire up your own thread and have a nice back-and-forth.
TnHepGuy
These aren't the thoughts of my "my-two-unerring-hepatologists" but rather what I put together from HR's previous posts on the subject as well as my own thoughts. I thought it useful for the group to have both points of view presented for his comments in the same thread. But yes, I'll be happy to step out of YOUR thread, as I have in the past if it makes you that uncomfortable. So no need to address me again like this because I will not respond.
Occult I think refers to cryptic, or hidden anything... so my take on occult virus is lurkers in the fat blobules, or something like that....but I could be wrong...its happened before...
fishdoc's correct, in that "occult" means something hidden.
In the context here, it refers to "hidden" virus - meaning virus that is below the level of detection in one's blood.
The Pham '06 paper posted above gives an overview of the subject and this definition: "<i>...the presence of replicating
HCV in persons who apparently completely recovered from
hepatitis C and whose sera were repeatedly negative for HCV
RNA by standard assays.</i>"
TnHepGuy
In the context here, it refers to "hidden" virus - meaning virus that is below the level of detection in one's blood.
The Pham '06 paper posted above gives an overview of the subject and this definition: "<i>...the presence of replicating
HCV in persons who apparently completely recovered from
hepatitis C and whose sera were repeatedly negative for HCV
RNA by standard assays.</i>"
TnHepGuy
MEDICAL PROFESSIONAL
Firstly, peace between at least the advanced members of this club seems to be important since some of the topics raised here go to the limits of human knowledge and extreme thoughtfulness and calmness is a minimum requirement for productive exchange of viewpoints.
Jmjm530s citations and interpretations are typically carefully worded and are appreciated by myself as a means to restrict my answer to additional fine tuning if necessary. There is often just too much to say in response and very little time. If misquoting would occur, I would promptly correct, but never to the point of nitpicking.
I studied the correspondence by Giannini and it basically reflects an analysis of the pathogenetic pathways that may lead to the well known HCV associated lymphoproliferative disorders and mixed cryoglobulinemia MC with specific reference to the now quite established occult HCV lymphoid tissue infection that persists - probably to a dramatically variable degree- even in sustained therapy responders. His particular point was that it is rather the persistence in the lymph tissue, not so much the interactions of liver HCV residuals that can lead to MC syndrome in SVR patients. This is cutting edge science and if you ask my opinion if any practical consequences are to be drawn from these observations from the perspective of a SVR that had or has again an MC syndrome(cryo titers) then the answwer is that for the intellectual that follows these developments carefully, like apparently you and willig, it is useful to keep keen understanding and approprate follow ups in mind, should the conclusion of these pathogenetic connections in the future be
to take preventative action against such lymphoproliferative and overstimulatory syndromes like e.g. a short course of antiviral therapy or - if and if a nontoxic HCV antiviral will be found - to use this just like it is done now with the prevention of herpes reoccurrence.
As for the subclinical insidious liver disease that might occur in some who - again in the future - might benefit from further antiviral supression of tissue bound virus, I refer to the previously mentioned monitoring and antifibrotic measures. For the average individual with SVR, Jims approach of living liver healthy and enjoy the quite obvious overall stability and benefits of SVR without constant worries will certainly be the standard approach to the patient that will question his hepatologist in this regard. On the other hand advanced thinking and proactive behaviour once the means for such emerge might save some of the few SVRs unlucky enough to have substantial health consequences from these viral residuals and/of the chronic immmune stimulation that they might cause.
Lastly, the fitness of some of such remnants or even a tiny fraction of such "residual virus" will sometimes be enough to bring the virus in the open again, particularly if immune compromising therapies need to be used.
In HBV, we already use fairly routinely antiviral protective therapy for every case of " inactive carrier" or even anti HBSAg pos patients, and continue it up to 6 month after immunosupression is stopped, to be safe. In HCV , it seems it is less likely to revert under these conditions. My guess is, again, once low toxicity HCV antivirals will become availabe some Drs will start using it for that purpose.
Jmjm530s citations and interpretations are typically carefully worded and are appreciated by myself as a means to restrict my answer to additional fine tuning if necessary. There is often just too much to say in response and very little time. If misquoting would occur, I would promptly correct, but never to the point of nitpicking.
I studied the correspondence by Giannini and it basically reflects an analysis of the pathogenetic pathways that may lead to the well known HCV associated lymphoproliferative disorders and mixed cryoglobulinemia MC with specific reference to the now quite established occult HCV lymphoid tissue infection that persists - probably to a dramatically variable degree- even in sustained therapy responders. His particular point was that it is rather the persistence in the lymph tissue, not so much the interactions of liver HCV residuals that can lead to MC syndrome in SVR patients. This is cutting edge science and if you ask my opinion if any practical consequences are to be drawn from these observations from the perspective of a SVR that had or has again an MC syndrome(cryo titers) then the answwer is that for the intellectual that follows these developments carefully, like apparently you and willig, it is useful to keep keen understanding and approprate follow ups in mind, should the conclusion of these pathogenetic connections in the future be
to take preventative action against such lymphoproliferative and overstimulatory syndromes like e.g. a short course of antiviral therapy or - if and if a nontoxic HCV antiviral will be found - to use this just like it is done now with the prevention of herpes reoccurrence.
As for the subclinical insidious liver disease that might occur in some who - again in the future - might benefit from further antiviral supression of tissue bound virus, I refer to the previously mentioned monitoring and antifibrotic measures. For the average individual with SVR, Jims approach of living liver healthy and enjoy the quite obvious overall stability and benefits of SVR without constant worries will certainly be the standard approach to the patient that will question his hepatologist in this regard. On the other hand advanced thinking and proactive behaviour once the means for such emerge might save some of the few SVRs unlucky enough to have substantial health consequences from these viral residuals and/of the chronic immmune stimulation that they might cause.
Lastly, the fitness of some of such remnants or even a tiny fraction of such "residual virus" will sometimes be enough to bring the virus in the open again, particularly if immune compromising therapies need to be used.
In HBV, we already use fairly routinely antiviral protective therapy for every case of " inactive carrier" or even anti HBSAg pos patients, and continue it up to 6 month after immunosupression is stopped, to be safe. In HCV , it seems it is less likely to revert under these conditions. My guess is, again, once low toxicity HCV antivirals will become availabe some Drs will start using it for that purpose.
My God, what a beautifully worded interpretation and post...what an asset you are to this board, not only in terms of your vast scientific knowledge....but your patience and finess in dealing with all the various personalities of this board....my hat's off to you...sorry, don't gush too often and I don't want to sound obsequious, but I just couldn't help myself here...thanks so much for all your help...
Wouldnt it be funny if HepResearchGuy turned out to be Spacecoast in disguise? Seriously though, HR, you missed your calling, family therapy might have been your natural calling. LOL. Can I ask a question about my 12 year old and her access to instant messaging? Any research on how long it takes a 12 year old to spontaneously blow up her father? Teenage kids cant be good for the liver.
Please help me out here.
If I remain PCR neg, and show a trace of cryo again, what do I accomplish by taking lets say a 6 month course of Peg/Riba again.
Apparently these leftovers in lymphoid tissue are just as resistant to more interferon as the leftovers in the liver.
But from reading previous posts, we can further reduce the load. Why should that be desirable...another 6 month of tx, vs a slightly lower load of trash virus.
By lowering that trash, do I reduce my chance of it ever coming back, do I help my liver further by having reduced the load, will that help me to get cryo neg again. And what do I gain by getting rid of the trace of cryo, since my cryo was not symptomatic in the first place.
Twotell is SVR, cryo neg at the end of tx, many month later had a trace of cryo, many month later cryo neg again.
His immune system must have gotten the residuals back to such a low level again, that they were just not enough to bring this abnormal immune response (cryo) about.
Six month ago I said I would do a short course again, now I say it's too much for me, remember how I boasted Willing.
Ina
If I remain PCR neg, and show a trace of cryo again, what do I accomplish by taking lets say a 6 month course of Peg/Riba again.
Apparently these leftovers in lymphoid tissue are just as resistant to more interferon as the leftovers in the liver.
But from reading previous posts, we can further reduce the load. Why should that be desirable...another 6 month of tx, vs a slightly lower load of trash virus.
By lowering that trash, do I reduce my chance of it ever coming back, do I help my liver further by having reduced the load, will that help me to get cryo neg again. And what do I gain by getting rid of the trace of cryo, since my cryo was not symptomatic in the first place.
Twotell is SVR, cryo neg at the end of tx, many month later had a trace of cryo, many month later cryo neg again.
His immune system must have gotten the residuals back to such a low level again, that they were just not enough to bring this abnormal immune response (cryo) about.
Six month ago I said I would do a short course again, now I say it's too much for me, remember how I boasted Willing.
Ina
It strikes me that in digesting all the questions and commentaries over the past week in relation to all the 'gray' areas surrounding HCV that we are in many ways still operating 'in the dark' We really know very little about issues like: residual virus and its impact long term, where the virus might hide/reside other than the liver and blood, why SVR's often experience a range of problems after seemingly successful therapy, what interferon does to alter the health and function of those who take it over long periods, or in multiple tx'es, how HCV might be transmitted other than the major routes, whether there is a tissue based infection that is transmitted to others without involving the blood, what causes occult virus in the liver for those who have no risk factors, etc. etc.
My point is that I am beginning to feel that I really understand less and less about this virus every year. There are just so many unanswered questions, fuzzy areas, controversial issues, and a complete lack of meaningful interventions or therepies for most of the 'other' issues surrounding HCV. We can treat it to get an undetected result in the blood, but beyond that we are all pretty much operating in the dark. We no longer really even understand what SVR means...where a few years ago it was cut and dried, it was the 'cure'. I start to get worn down trying to contemplate all the new understandings about the virus, and how we might make practical use of any of this knowledge.
I don't know about all of you, but I start to feel like I am talking myself in circles. Lots of energy and brainpower is being expended, to no apparent end. Depressing. And what's worse, the mainstream HCV medical community is barely involved (or interested) in these issues.
DoubleDose
My point is that I am beginning to feel that I really understand less and less about this virus every year. There are just so many unanswered questions, fuzzy areas, controversial issues, and a complete lack of meaningful interventions or therepies for most of the 'other' issues surrounding HCV. We can treat it to get an undetected result in the blood, but beyond that we are all pretty much operating in the dark. We no longer really even understand what SVR means...where a few years ago it was cut and dried, it was the 'cure'. I start to get worn down trying to contemplate all the new understandings about the virus, and how we might make practical use of any of this knowledge.
I don't know about all of you, but I start to feel like I am talking myself in circles. Lots of energy and brainpower is being expended, to no apparent end. Depressing. And what's worse, the mainstream HCV medical community is barely involved (or interested) in these issues.
DoubleDose
<u>Ina</u> - if your goal in an attempted re-tx is to try and eliminate cryo (as opposed to occult), you're off in uncharted turf (once again) with no guidelines (i.e. - studies/trials) to measure against. You could consult a specialist(s) to get a take on if it would be even worth the attempt to try and reach fully clear (eg - what would be the benefits of being long-term cryo-free vs. potential costs of being long-term low-level cryo and asymptomatic? - not to mention the potential costs of the tx itself). And as well as interferon you could discuss the possibility of tx via rituximab, too.
<u>DD</u> - I don't see it as depressing, per se. Rather, I tend to see myself as being frustrated/impatient for more/new research to come forward on the subject matters of interest. We'd all love for some solid, concrete answers to replace the minuscule, malleable data that currently exists.
TnHepGuy
<u>DD</u> - I don't see it as depressing, per se. Rather, I tend to see myself as being frustrated/impatient for more/new research to come forward on the subject matters of interest. We'd all love for some solid, concrete answers to replace the minuscule, malleable data that currently exists.
TnHepGuy
the way i see it, SVR has stopped the onslaught of hcv on my liver, so hepatitis is cured. Is it enough to keep HCC at bay? No one knows, but why worry about a meteor light years away? What reward would that bring? What kind of preparation can you make?
If my daughter's perennial rhinitis is somehow caused by an unknown way of transmission of hcv, or if I was to start worrying about that, it would be a complete waste of my energy and I would be forgoing the actual proven allergies to dust and pollen. Her aches and rhinitis pose daily discomfort, but does not incapacitate her in any way and it is treatable. None of her complaints pose a health risk, no more than any exposure to the other childhood viruses, or new influenzas.
Same for me, any possible 'occult' virus poses no health concerns to me. The durability of SVR tells me that worrying about it is a misdirection of my energy. Thousands of people that treated had to have been exposed to steroids, chemotherapy, treatment for trauma and other injuries and conditions at some point in the 10+ years from EOT, and I have not read of many late relapses happening. Can't cross bridges until you get to them, so why stress before?
Is somehow residual virus stimulating my system and perpetuating my joint aches and occassional fog? Maybe, but again, this is not a severe health issue, it brings no reward to worry about an abstract risk. This worry has become an obsession and a source of stress for many, and we know how bad stress can be on your health. I think the minimization of stress would be a more productive focus, than on an abstract health risk. Stress might get your heart or brain (with a stroke) before the occult/residual virus gets anything out of us.
People that are not SVR and are in cirrhosis have a more valid health concern, than us SVRs with a hypothetical hidden virus. Hypothetical because none of us, but Mikesimon, have tested positive for non serum HCV.
With hepatitis gone, do I worry about residual HCV causing HCC or some other less deadly condition? No, not until it happens, if it does.
If my daughter's perennial rhinitis is somehow caused by an unknown way of transmission of hcv, or if I was to start worrying about that, it would be a complete waste of my energy and I would be forgoing the actual proven allergies to dust and pollen. Her aches and rhinitis pose daily discomfort, but does not incapacitate her in any way and it is treatable. None of her complaints pose a health risk, no more than any exposure to the other childhood viruses, or new influenzas.
Same for me, any possible 'occult' virus poses no health concerns to me. The durability of SVR tells me that worrying about it is a misdirection of my energy. Thousands of people that treated had to have been exposed to steroids, chemotherapy, treatment for trauma and other injuries and conditions at some point in the 10+ years from EOT, and I have not read of many late relapses happening. Can't cross bridges until you get to them, so why stress before?
Is somehow residual virus stimulating my system and perpetuating my joint aches and occassional fog? Maybe, but again, this is not a severe health issue, it brings no reward to worry about an abstract risk. This worry has become an obsession and a source of stress for many, and we know how bad stress can be on your health. I think the minimization of stress would be a more productive focus, than on an abstract health risk. Stress might get your heart or brain (with a stroke) before the occult/residual virus gets anything out of us.
People that are not SVR and are in cirrhosis have a more valid health concern, than us SVRs with a hypothetical hidden virus. Hypothetical because none of us, but Mikesimon, have tested positive for non serum HCV.
With hepatitis gone, do I worry about residual HCV causing HCC or some other less deadly condition? No, not until it happens, if it does.
the data in <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16628675&query_hl=6&itool=pubmed_docsum">Giannini'06</a> is very limited (9 patients) and RNA detection was via "homemade" screens. Though HR did not seem to find fault with their report it presumably remains a very preliminary finding until observed in a larger group of patients with more widely calibrated PBMC RNA assays. It *is* interesting because it seems to give evidence of a strong correlation between HCV lymph infection and MC regardless of liver infection or SVR status, but there's so little data the authors don't even give a statistical significance value and only suggest "Further studies investigating the possible role played by lymphatic infection in HCV is important". Furthermore, to the best of my knowledge, there is zero data at present that continued ifn tx has any effect whatsoever on residual virus.
The fact that you're reluctant to sign up for 6 more months of hell is very, very, very, good news! Like many others, I really do believe that SVR=(enough CURE for one lifetime). The puzzlement over the mysterious ways of this virus is really another story altogether from the pragmatic question of trying to stop it from killing you.
The fact that you're reluctant to sign up for 6 more months of hell is very, very, very, good news! Like many others, I really do believe that SVR=(enough CURE for one lifetime). The puzzlement over the mysterious ways of this virus is really another story altogether from the pragmatic question of trying to stop it from killing you.
you said: Furthermore, to the best of my knowledge, there is zero data at present that continued ifn tx has any effect whatsoever on residual virus.
As far as I can determine, the residual virus seems to be a part of the landscape for ALL tx'ers...the 12 week courses, the 24, 48 and 72 week tx'ers. I would expect it to be there after a 3 year tx as well. I would think that the residual virus is nothing more than a virus being pushed back past the point of active infection, into remission. That may be as good as it gets, under any circumstances. Horrible to contemplate, but it might just be the way this virus works. Maybe it becomes a permanent part of our bodily makeup, in a way, and cannot be extracted, eradicated, exterminated or whatever. If I had to make a big bet, that is where my money would go. I just hope that by the virus being in remission that it really is in REMISSION, not just reduced to a lower level infection with ongoing damage. I guess we will all find out the answer in due time.
Stay well.
DoubleDose
As far as I can determine, the residual virus seems to be a part of the landscape for ALL tx'ers...the 12 week courses, the 24, 48 and 72 week tx'ers. I would expect it to be there after a 3 year tx as well. I would think that the residual virus is nothing more than a virus being pushed back past the point of active infection, into remission. That may be as good as it gets, under any circumstances. Horrible to contemplate, but it might just be the way this virus works. Maybe it becomes a permanent part of our bodily makeup, in a way, and cannot be extracted, eradicated, exterminated or whatever. If I had to make a big bet, that is where my money would go. I just hope that by the virus being in remission that it really is in REMISSION, not just reduced to a lower level infection with ongoing damage. I guess we will all find out the answer in due time.
Stay well.
DoubleDose
Ivette telling somebody like myself...take your SVR and forget about the rest, is not going to work.
Like the virus, I was programmed to make a trillion worry cells, and my immune system is overwhelmed :)
Now I am not sitting all day around, planning war against residuals, but with todays information, I like to have a battle plan which I change according to the new info emerging.
Look at HR statement, PROACTIVE is the word here:
On the other hand advanced thinking and proactive behaviour once the means for such emerge might save some of the few SVRs unlucky enough to have substantial health consequences from these viral residuals and/of the chronic immmune stimulation that they might cause.
Lastly, the fitness of some of such remnants or even a tiny fraction of such "residual virus" will sometimes be enough to bring the virus in the open again, particularly if immune compromising therapies need to be used.
---------------------
I agree that re-tx in order to decrease remnant viral load further does not accomplish much, nor does bringing an a-symptomatic cryo patient to undetected again.
But the way I understand HR, he seems to think that under certain circumstances it might not be a bad idea, to do a short course of Interferon for the purpose of DEGRADING the virus again.
The more degraded, the less likely they will be able to reproduce.
As a matter of fact, that idea appeals to me a lot.
What circumstance could lead to that, immunosuppression, either with chemo or prednisone.
I slugged it out for over 2 years on tx, why would I want to take the chance, that even though unlikely, yet possible, the virus could resurface.
All I am saying, it's worth a thought. Should I have to undergo any of the above mentioned tx, maybe hanging on a few month of peg/riba would knock any strong arms back into submission.
This may look to others like I am stressing out over this.
But I am comforted by the knowledge, that I have my thoughts in order on this issue...if that makes any sense.
No willing, I am not re-tx if cryo returns, and won't with slightly elevated Alt's or GGT's.
But what if they should rise for extended period of times into 70, 80, or so. Would you stand by and just watch?
Tnguy...getting rid of Cryo with Rituxan would be a bandaide. I think it would ultimately come back. If I were symtomatic cryo, I would do combo and Rituxan, just like twotells did.
DD, I can add something to the list of post tx issues, allergies. I was diagnosed with gluten allergy, no diagnosis of Celiac though. Symptoms started about 3 moth post tx. I had no allergies before tx, and no...it's not old age.
The other thing is my body temp. I vaguely remember taking it at some point after tx, and it had gone up to approx. 97.5 and afterwards I forgot about it.
Many times when we visit a doc, they routinely take our temp.
Well, I have gotten questions from RNs and other physicians help about my low temp. Turns out my temp is usually between 96.3 and 96.7. That is lower then what it was on combo. I have been freezing for a long time, and wondered why I was able to endure 100F this summer without any complaints.
My temp was normal before tx around 98.6.
Do I have to convince you that this is not old age :)
I too am overwhelmed with occult and it's implications. I have information overlood, but rather suffer from overload then underload.
There are no if's or but's about it, there is no option for me... I can not walk into SVR sunshine, unless I also keep abreast of what's going on behind the scene.
Thank's everyone for chiming in,
Ina
Like the virus, I was programmed to make a trillion worry cells, and my immune system is overwhelmed :)
Now I am not sitting all day around, planning war against residuals, but with todays information, I like to have a battle plan which I change according to the new info emerging.
Look at HR statement, PROACTIVE is the word here:
On the other hand advanced thinking and proactive behaviour once the means for such emerge might save some of the few SVRs unlucky enough to have substantial health consequences from these viral residuals and/of the chronic immmune stimulation that they might cause.
Lastly, the fitness of some of such remnants or even a tiny fraction of such "residual virus" will sometimes be enough to bring the virus in the open again, particularly if immune compromising therapies need to be used.
---------------------
I agree that re-tx in order to decrease remnant viral load further does not accomplish much, nor does bringing an a-symptomatic cryo patient to undetected again.
But the way I understand HR, he seems to think that under certain circumstances it might not be a bad idea, to do a short course of Interferon for the purpose of DEGRADING the virus again.
The more degraded, the less likely they will be able to reproduce.
As a matter of fact, that idea appeals to me a lot.
What circumstance could lead to that, immunosuppression, either with chemo or prednisone.
I slugged it out for over 2 years on tx, why would I want to take the chance, that even though unlikely, yet possible, the virus could resurface.
All I am saying, it's worth a thought. Should I have to undergo any of the above mentioned tx, maybe hanging on a few month of peg/riba would knock any strong arms back into submission.
This may look to others like I am stressing out over this.
But I am comforted by the knowledge, that I have my thoughts in order on this issue...if that makes any sense.
No willing, I am not re-tx if cryo returns, and won't with slightly elevated Alt's or GGT's.
But what if they should rise for extended period of times into 70, 80, or so. Would you stand by and just watch?
Tnguy...getting rid of Cryo with Rituxan would be a bandaide. I think it would ultimately come back. If I were symtomatic cryo, I would do combo and Rituxan, just like twotells did.
DD, I can add something to the list of post tx issues, allergies. I was diagnosed with gluten allergy, no diagnosis of Celiac though. Symptoms started about 3 moth post tx. I had no allergies before tx, and no...it's not old age.
The other thing is my body temp. I vaguely remember taking it at some point after tx, and it had gone up to approx. 97.5 and afterwards I forgot about it.
Many times when we visit a doc, they routinely take our temp.
Well, I have gotten questions from RNs and other physicians help about my low temp. Turns out my temp is usually between 96.3 and 96.7. That is lower then what it was on combo. I have been freezing for a long time, and wondered why I was able to endure 100F this summer without any complaints.
My temp was normal before tx around 98.6.
Do I have to convince you that this is not old age :)
I too am overwhelmed with occult and it's implications. I have information overlood, but rather suffer from overload then underload.
There are no if's or but's about it, there is no option for me... I can not walk into SVR sunshine, unless I also keep abreast of what's going on behind the scene.
Thank's everyone for chiming in,
Ina
<u>willing</u> - you had mentioned above: "<i>...to the best of my knowledge, there is zero data at present that continued ifn tx has any effect whatsoever on residual virus.</i>"
The <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16611276&query_hl=2&itool=pubmed_docsum">Pardo '06</a> paper looks at a somewhat limited (10 patients doing a 24 week course) tx'ing of occult. The results they get show a 30% "sustained response" and a 5 out-of 5 positive bx for HCV RNA, though the overall viral load decreased. 3 out-of 5 had a decrease in necroinflammation and fibrosis.
<u>Ina</u> - some things to consider in any talk of a re-tx with combo to go after occult: 1.) might be very tough to find a doc to agree to participate; 2.) might be even that much tougher to find an insurance company to foot the bill.
There's just so little out there on occult that the vast majority of doc's wouldn't go out on a limb to go after it. And most (all?) insurance companies aren't going to shell out based upon lack of info and no medical community push to tx.
TnHepGuy
The <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16611276&query_hl=2&itool=pubmed_docsum">Pardo '06</a> paper looks at a somewhat limited (10 patients doing a 24 week course) tx'ing of occult. The results they get show a 30% "sustained response" and a 5 out-of 5 positive bx for HCV RNA, though the overall viral load decreased. 3 out-of 5 had a decrease in necroinflammation and fibrosis.
<u>Ina</u> - some things to consider in any talk of a re-tx with combo to go after occult: 1.) might be very tough to find a doc to agree to participate; 2.) might be even that much tougher to find an insurance company to foot the bill.
There's just so little out there on occult that the vast majority of doc's wouldn't go out on a limb to go after it. And most (all?) insurance companies aren't going to shell out based upon lack of info and no medical community push to tx.
TnHepGuy
thanks for the link, but as I read it, Pardo'06 doesn't address the question of whether further combo-tx does anything for residual virus since their patient selection required that <em>"None of the patients could have received anti-viral therapy before the inclusion in the study"</em>.
This gets back to the distinction beteween occult (serum-UND and no HCVab) vs residual (serum-UND, HCVab present, cell HCV present).
Two other thoughts:
(1) Pardo'06 can also be interpreted as evidence (though circumstantial) that the low-level liver HCV infection in some is up to no good insofar as all patients selected exhibited out-of range ALTs for 12 months and <em>"presence of necroinflammatory activity in liver biopsy performed within 1 year before the study entry"</em>. However, my read of their Table 1 is that 1 patient was an F2 and all others were F0 or F1.
(2) <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17051492&query_hl=3&itool=pubmed_docsum">Castillo'06</a>
in discussing the difference between the frequency of RNA (-) strand detection (and thus of detectable viral replication in liver cells) in his data (95%) vs Radkowski's (27%), includes the speculation that <em>"Thus, intrahepatic levels of positive- and negative-strand HCV RNA might decrease over time, becoming undetectable in sustained responders"</em>. Maybe all that's required is a little (more) patience...
This gets back to the distinction beteween occult (serum-UND and no HCVab) vs residual (serum-UND, HCVab present, cell HCV present).
Two other thoughts:
(1) Pardo'06 can also be interpreted as evidence (though circumstantial) that the low-level liver HCV infection in some is up to no good insofar as all patients selected exhibited out-of range ALTs for 12 months and <em>"presence of necroinflammatory activity in liver biopsy performed within 1 year before the study entry"</em>. However, my read of their Table 1 is that 1 patient was an F2 and all others were F0 or F1.
(2) <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17051492&query_hl=3&itool=pubmed_docsum">Castillo'06</a>
in discussing the difference between the frequency of RNA (-) strand detection (and thus of detectable viral replication in liver cells) in his data (95%) vs Radkowski's (27%), includes the speculation that <em>"Thus, intrahepatic levels of positive- and negative-strand HCV RNA might decrease over time, becoming undetectable in sustained responders"</em>. Maybe all that's required is a little (more) patience...
I also want to make a distinction between 'Occult' virus, and 'Residual' virus. I think the easiest way is to describe the general circumstance for each:
Residual Virus is that virus found in those who have treated and achieved SVR, and also potentially in those who spontaneously cleared the virus. The residual virus is most commonly found in very minute quantities in PCMB's, lymphatic tissue, and sometimes in minute quantities in the liver. It may also be in other cells, and organs, but not enough research has been done at this point. This 'residual' virus is controversial, and so far has not shown itself to be a serious threat to the tissues, or cells that it resides in. The liver is generally not inflamed, and the LFT's are almost always normal. There is no sign of ongoing liver disease. It appears 'benign'.
Occult Virus, on the other hand, is usually referred to in cases where there are abnormal LFT's, and a lack of antibodies in the serum, and no trace of the virus by PCR in the blood. These are chiefly people who have not treated, and are not considered to be spontaneous clearers either, since there is no HCV antibody in the blood. They come to the attention of their doctors because of their abnormal LFT's. The virus residing in their livers is active, as in the typical HCV blood/liver infection, and it is chronic. Generally there is ongoing damage being done, and obvious inflammation, as evidenced by the LFT's.
A good percentage of Occult HCV infected persons are those with a history of intravenous drug use.
This is my understanding of residual vs. occult.
One is a 'benign' viral infection in somewhat of a dormant stage. The other is active, destructive, chiefly in the liver, and often needs to be treated. On the other hand, Residual viral infection, by its very definition, shows no sign of going away, regardless of treatment length.
DoubleDose
Residual Virus is that virus found in those who have treated and achieved SVR, and also potentially in those who spontaneously cleared the virus. The residual virus is most commonly found in very minute quantities in PCMB's, lymphatic tissue, and sometimes in minute quantities in the liver. It may also be in other cells, and organs, but not enough research has been done at this point. This 'residual' virus is controversial, and so far has not shown itself to be a serious threat to the tissues, or cells that it resides in. The liver is generally not inflamed, and the LFT's are almost always normal. There is no sign of ongoing liver disease. It appears 'benign'.
Occult Virus, on the other hand, is usually referred to in cases where there are abnormal LFT's, and a lack of antibodies in the serum, and no trace of the virus by PCR in the blood. These are chiefly people who have not treated, and are not considered to be spontaneous clearers either, since there is no HCV antibody in the blood. They come to the attention of their doctors because of their abnormal LFT's. The virus residing in their livers is active, as in the typical HCV blood/liver infection, and it is chronic. Generally there is ongoing damage being done, and obvious inflammation, as evidenced by the LFT's.
A good percentage of Occult HCV infected persons are those with a history of intravenous drug use.
This is my understanding of residual vs. occult.
One is a 'benign' viral infection in somewhat of a dormant stage. The other is active, destructive, chiefly in the liver, and often needs to be treated. On the other hand, Residual viral infection, by its very definition, shows no sign of going away, regardless of treatment length.
DoubleDose
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