Aa
A few questions for 'hepatitisresearcher' re: occult
1.) - is it possible that occult in post-SVR patients (I've seen the term Secondary Occult Infection (SOI) used to differentiate post-SVR's from those occult patients with no known tx profile (Primary Occult Infection (POI)), so I'll use these terms) is a resistant form of Hep C occult virus, whereas in POI patients it wouldn't be since there has been no resistive selection via tx? Either way, this paper <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">Effect of anti-viral therapy for occult hepatitis C virus infection</a> shows a low response rate to combo (30%) and a 100% continuing RNA in bx'ed livers (5 of 5). (I can't tell from the abstract if the patients here were POI or SOI).
2.) - the above study, as well as this one using 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">Hepatitis C virus replicates in the liver of patients who have a sustained response to antiviral treatment</a>, both discuss occult patients having continuing ongoing necroinflammation. While I imagine it is theoretically possible that a relatively low level of inflammation could be 'overcome' via the liver's self-healing mechanisms, would you think there might be liver-related consequences of such chronic inflammation (eg - fibrosis. Or at the very least, a lessening of the ability of the liver to heal)? Could this possibly put an occult patient at greater risk for HCC?
2.) - the above study, as well as this one using 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">Hepatitis C virus replicates in the liver of patients who have a sustained response to antiviral treatment</a>, both discuss occult patients having continuing ongoing necroinflammation. While I imagine it is theoretically possible that a relatively low level of inflammation could be 'overcome' via the liver's self-healing mechanisms, would you think there might be liver-related consequences of such chronic inflammation (eg - fibrosis. Or at the very least, a lessening of the ability of the liver to heal)? Could this possibly put an occult patient at greater risk for HCC?
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
-----------------------------------
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: SOMETHING HAS TO HOLD THESE VIRIONS BACK FROM GROWING BACK TO THEIR TRILLION STAGE. What would it be ...(without interferon*)
-----------------------------------------
*my addition
-------------------------------------------
As it was explained to me by one hepatologist -- and I can't guarantee I'm going to repeat this correctly -- with SVR under SOC the virus is either gone or left in what I believe you described in an earlier post in a "trashed" state. Not really complete. Remnants. No real threat. Or as even most of the occult/persistent virus papers state "no clinical significance proven".
Therefore, I assume if we can get to the same non-detectible state without interferon -- say for example with this cocktail -- that the same might hold true, which then might leave the immune system off the hook so to speak. Even with severly impaired immune systems, I believe there are only one or two documented cases of relapse after several years of SVR.
It's hard to believe that no one is doing limited tests without interferon or a similar agents with all the newer drugs out there. At one point not that long ago, Vertex hinted it might but never did. Do you think a non-interferon approach will be tested soon?
-- Jim
-----------------------------------------
*my addition
-------------------------------------------
As it was explained to me by one hepatologist -- and I can't guarantee I'm going to repeat this correctly -- with SVR under SOC the virus is either gone or left in what I believe you described in an earlier post in a "trashed" state. Not really complete. Remnants. No real threat. Or as even most of the occult/persistent virus papers state "no clinical significance proven".
Therefore, I assume if we can get to the same non-detectible state without interferon -- say for example with this cocktail -- that the same might hold true, which then might leave the immune system off the hook so to speak. Even with severly impaired immune systems, I believe there are only one or two documented cases of relapse after several years of SVR.
It's hard to believe that no one is doing limited tests without interferon or a similar agents with all the newer drugs out there. At one point not that long ago, Vertex hinted it might but never did. Do you think a non-interferon approach will be tested soon?
-- Jim
Context relevant research seems quite, well, relevant to the issues at hand. Thanks again for this invaluable input.
What clinical followup, if any, would you recommend for patients who have been categorized as attaining SVR, especially those for whom further biopsies (to r/o HCV RNA in liver tissue) are highly unlikely?
You have mentioned some research of OTC immune stimulants at AGI. Did any look especially promising to you? What about lactoferrin, which a poster mentioned today? Others? Any thoughts on maintaining strong immune response post-treatment, especially when treatment has triggered chronic autoimmune conditions of various sorts?
What clinical followup, if any, would you recommend for patients who have been categorized as attaining SVR, especially those for whom further biopsies (to r/o HCV RNA in liver tissue) are highly unlikely?
You have mentioned some research of OTC immune stimulants at AGI. Did any look especially promising to you? What about lactoferrin, which a poster mentioned today? Others? Any thoughts on maintaining strong immune response post-treatment, especially when treatment has triggered chronic autoimmune conditions of various sorts?
MEDICAL PROFESSIONAL
Well that is all part of what is discussed here. So the durability question of SVR probably depends on
a) how crippled the remnants are ( remember the importance of riba to overmutate) see above:
" a sign that the remaining virus at least does not replicate at any substantial rate. In other words its replication efficiency - if any - is very low, since the residual virus found in the liver is not so ultralow as the plasma virion level. That part is good news and probably partly causes the stability of SVR"
b) How well the memory immune supression works. This will depend in turn on the general functionality of the immune system, the extent it has focused on the virus, the extent to which ( because of all the mutations in that remnant trash virus) the viral residuals still display relevant epitopes ( class I 10aa on the liver cells, class II ( 20 aa length viral breakdown peptides) through macrophages and dendritics that uptake and digest viral material from dying cells and otherwise. It might also paradoxically depend on the very quantity of that residual to keep it on constant alert, as we see this all the time in HBV. Supress the virus too much with antivirals - immune system looses interest - no more antiviral - no suffcient memory cells around - virus comes back real high- now a new flare hits. This seem to be also sometimes the case with HCV after treatment stops. ( Thats when post tx the ALTs go really high - same scenario.}
a) how crippled the remnants are ( remember the importance of riba to overmutate) see above:
" a sign that the remaining virus at least does not replicate at any substantial rate. In other words its replication efficiency - if any - is very low, since the residual virus found in the liver is not so ultralow as the plasma virion level. That part is good news and probably partly causes the stability of SVR"
b) How well the memory immune supression works. This will depend in turn on the general functionality of the immune system, the extent it has focused on the virus, the extent to which ( because of all the mutations in that remnant trash virus) the viral residuals still display relevant epitopes ( class I 10aa on the liver cells, class II ( 20 aa length viral breakdown peptides) through macrophages and dendritics that uptake and digest viral material from dying cells and otherwise. It might also paradoxically depend on the very quantity of that residual to keep it on constant alert, as we see this all the time in HBV. Supress the virus too much with antivirals - immune system looses interest - no more antiviral - no suffcient memory cells around - virus comes back real high- now a new flare hits. This seem to be also sometimes the case with HCV after treatment stops. ( Thats when post tx the ALTs go really high - same scenario.}
MEDICAL PROFESSIONAL
See all these mechanistic ideas basically serve the purpose to get a feel for the size of the problem. What matters most are the facts - the bottom line and so far so good. But with chemo or immunsupressive antirheumatic therapy the relapsers will likely increase and prophylaxis will be needed. New drugs coming up will hopefully do that.
HR: Supress the virus too much with antivirals - immune system looses interest - no more antiviral - no suffcient memory cells around - virus comes back real high
---------------------------------------------------
What about those that suggest that sometimes in the future a cocktail of antivirals may be the eventual tx, as like with HIV? If this cocktail does work out, wouldn't this contradict the theory of "immune system losing interest" since no interferon is being used. I know you shared with us some doubts previously at least with VX-950 without interferon. Do you have these same doubts with a cocktail? I guess time will tell on this.
-----------
As to the durability of SVR, recent studies suggest it is durable up to ten years out, the ten year number only because that is how long SVRs has been studied.
Rev suggests (and if I misquote, please correct me Rev) that since the data is only ten years out we can't say SVR is durable for longer. I say, there's no reason to believe that SVR won't be durable for longer than ten years based. I do understand both statements can be correct, but given you studies of the immune system, curious what your take is how meaningful a ten year period is in terms of viral suppression. In other words, if studies show that the virus has been suppressed for ten years in SVRs, do you think like in five or ten years we will start having an avalanche of relapsers? Beyond that, some of us oldens -- not sure how old Rev is -- will be too old to care. LOL.
Thanks for any input on this.
-- Jim
---------------------------------------------------
What about those that suggest that sometimes in the future a cocktail of antivirals may be the eventual tx, as like with HIV? If this cocktail does work out, wouldn't this contradict the theory of "immune system losing interest" since no interferon is being used. I know you shared with us some doubts previously at least with VX-950 without interferon. Do you have these same doubts with a cocktail? I guess time will tell on this.
-----------
As to the durability of SVR, recent studies suggest it is durable up to ten years out, the ten year number only because that is how long SVRs has been studied.
Rev suggests (and if I misquote, please correct me Rev) that since the data is only ten years out we can't say SVR is durable for longer. I say, there's no reason to believe that SVR won't be durable for longer than ten years based. I do understand both statements can be correct, but given you studies of the immune system, curious what your take is how meaningful a ten year period is in terms of viral suppression. In other words, if studies show that the virus has been suppressed for ten years in SVRs, do you think like in five or ten years we will start having an avalanche of relapsers? Beyond that, some of us oldens -- not sure how old Rev is -- will be too old to care. LOL.
Thanks for any input on this.
-- Jim
MEDICAL PROFESSIONAL
The answer to the first part is as above
" Therefore watching lifestyle, antifibrotic concepts and measures, LFTs, platelets, and fibrosis extent itself will be quite important. It looks like Echosens will have a bright future.
HCC is another issue that needs to be watched, unfortunately, with regulart AFPs, 6month ultrasounds."
the issue of OTC immune stimulants and o/or antifibrotics is too complex and also too important to answer in a nutshell. Will bring this up in a structured format another time. Lactoferrin is part of the formula "likely to have some benefit, unlikely to hurt"
Meanwhile I would like for everyone interested in that subject on how damaging circumstances ( like mild chronic inflammation) can be uncoupled from the pathognetic consequences to take a look at last weeks famous nature paper regarding the prevention of chronic pathology by severe obesity through resveratrol in mice. Look how it prevented liver disease. There is a ton of relevant wisdom in there for hepatitis patients, not just obese ones.
" Therefore watching lifestyle, antifibrotic concepts and measures, LFTs, platelets, and fibrosis extent itself will be quite important. It looks like Echosens will have a bright future.
HCC is another issue that needs to be watched, unfortunately, with regulart AFPs, 6month ultrasounds."
the issue of OTC immune stimulants and o/or antifibrotics is too complex and also too important to answer in a nutshell. Will bring this up in a structured format another time. Lactoferrin is part of the formula "likely to have some benefit, unlikely to hurt"
Meanwhile I would like for everyone interested in that subject on how damaging circumstances ( like mild chronic inflammation) can be uncoupled from the pathognetic consequences to take a look at last weeks famous nature paper regarding the prevention of chronic pathology by severe obesity through resveratrol in mice. Look how it prevented liver disease. There is a ton of relevant wisdom in there for hepatitis patients, not just obese ones.
MEDICAL PROFESSIONAL
you wrote
What about those that suggest that sometimes in the future a cocktail of antivirals may be the eventual tx, as like with HIV? If this cocktail does work out, wouldn't this contradict the theory of "immune system losing interest" since no interferon is being used. I know you shared with us some doubts previously at least with VX-950 without interferon. Do you have these same doubts with a cocktail?
It will depend on how active the immune system already participated in the fight against the virus before TX. You hinted this correctly before: A low viral load indicates that the spontaneous inner defenses are already working better, that why you advocated "hit when low VL, when your body is on your side".
In HBV the immune system is typically more active against the virus ( even in chronic HBV). But, in the e-antigen neg hepatitis b, when you let people off antivirals - totally UND!!!- they come back like clockwork. LIFELONG THERAPY IS NOW THE BUZZWORD! in these, particularly if they had advanced liver problems.
Thus it is my unpleasant guess that no ifn/riba based cocktails will nicely supress the virus to UND, but SVR might be much harder to obtain. It all depends on that residual Jim: SOMETHING HAS TO HOLD THESE VIRIONS BACK FROM GROWING BACK TO THEIR TRILLION STAGE. What would it be ... full circle .. see above concepts.. see the importance of IFN and riba in them.
How many virions are necessary to INTERNALLY reinfect a body/liver into full bloom: ONE CAPABLE VIRION.
An interesting phantasy?
In the chimp studies I have mentioned (Vancouver meeting)we saw with horror that indeed 1 virion of HBV iv was able to infect these poor humanoids. There were also HCV infections of these chimps done .. but that we will discuss another tiime.
.
What about those that suggest that sometimes in the future a cocktail of antivirals may be the eventual tx, as like with HIV? If this cocktail does work out, wouldn't this contradict the theory of "immune system losing interest" since no interferon is being used. I know you shared with us some doubts previously at least with VX-950 without interferon. Do you have these same doubts with a cocktail?
It will depend on how active the immune system already participated in the fight against the virus before TX. You hinted this correctly before: A low viral load indicates that the spontaneous inner defenses are already working better, that why you advocated "hit when low VL, when your body is on your side".
In HBV the immune system is typically more active against the virus ( even in chronic HBV). But, in the e-antigen neg hepatitis b, when you let people off antivirals - totally UND!!!- they come back like clockwork. LIFELONG THERAPY IS NOW THE BUZZWORD! in these, particularly if they had advanced liver problems.
Thus it is my unpleasant guess that no ifn/riba based cocktails will nicely supress the virus to UND, but SVR might be much harder to obtain. It all depends on that residual Jim: SOMETHING HAS TO HOLD THESE VIRIONS BACK FROM GROWING BACK TO THEIR TRILLION STAGE. What would it be ... full circle .. see above concepts.. see the importance of IFN and riba in them.
How many virions are necessary to INTERNALLY reinfect a body/liver into full bloom: ONE CAPABLE VIRION.
An interesting phantasy?
In the chimp studies I have mentioned (Vancouver meeting)we saw with horror that indeed 1 virion of HBV iv was able to infect these poor humanoids. There were also HCV infections of these chimps done .. but that we will discuss another tiime.
.
As for the 10 year durability question;
A lot depends on the sample size, but
If the durability of SVR would have a mean of say 12 years, one would expect to see a statistical indication of this within the study sample.
My guess is that if there is a breakdown of SVR, we should see that happening in individuals who are unfortunate to be in the one standard deviation below the mean.
A lot depends on the sample size, but
If the durability of SVR would have a mean of say 12 years, one would expect to see a statistical indication of this within the study sample.
My guess is that if there is a breakdown of SVR, we should see that happening in individuals who are unfortunate to be in the one standard deviation below the mean.
MEDICAL PROFESSIONAL
This all is a new and unpleasant issue that i have commented on a few times. But you have specific questions beyond that.
it is not surprising that therapy can reduce the small amount of virus in occult infection further downwards, but also that there is still no complete eradication.we could take the UND VL that is part of the defintion of the sundrome as a sign that the remaining virus at least does not replicate at any substantial rate. In other words its replication efficiency - if any - is very low, since the residual virus found in the liver is not so ultralow as the plasma virion level. That part is good new and reflects the stability of SVR.
The idea of a distinction between resistant occult virus past SVR vs "nonresistant" as in "primary occult" raises the question RESISTANCE TO WHAT?. the fact that these residuals exist -as now becoming an accepted fact fast- means that they are resistant to eradication for a host of reasons eg that they sit in a liver cell and were able to turn off the antiviral mechanisms inside that very cell, but at price to their fitness nd capacity to reinfect and many more reasons.
But overall the SVR residuals are more likely to carry resistance to further eradication by IFN than the primary occult ones.
The extent to which this lingering HCV presence can cause prolonged liver damage like fibrosis will certainly be studied intensely in the near future and will turn out to be quite different among individual SVRs from nothing to substantial progression. Therefore watching lifestyle, antifibrotic concepts and measures, LFTs and fibrosis extent itself will be quite important. It looks like Echosens will have a bright future.
HCC is another issue that needs to be watched, unfortunately.
Likewise we know that even the "300 000 000 inactive HBV carriers" have an increased rate of HCC compared to non hep controls. Quantitative comparisons of risk cannot easily be drawn, since the two viruses have substantial differences in their oncogenic mechanisms (B has the "x" gene and a double stranded DNA minichromosome (cccDNA), ready to integrate in the liver genome each time a division takes place....
Thus these advanced questions have only a small lit base to support any notions.
Here is another CONTEXT PERTINENT abstract from pubmed (LIKE PUBLIC MED AND NOT COPYRIGHTPROTECTED BUT HERE TO BE USED TO THE BENEFIT OF ANYONE SO VERY MUCH HERE)
Med Klin (Munich). 2006 May 15;101(5):378-83.
[Virus persistence in hepatitis C: lifelong infection despite therapy?]
[Article in German]
Gockel HR, Heidemann J, Lugering N.
Medizinische Klinik, St. Marien-Hospital Hamm, Hamm. ***@****
BACKGROUND: Chronic hepatitis C infection still represents a clinical and
scientific challenge. Exciting progress has been achieved by the use of combined
therapy regimens with pegylated interferon and ribavirin resulting in sustained
virological response rates of 60-80%, depending on the genotype. VIRUS
PERSISTENCE DESPITE SUCCESSFUL THERAPY: Despite favorable longterm data with
regard to viremia, liver histology and serum liver enzymes in treated patients
who comply with the criteria of sustained virological response, a complete
elimination of the hepatitis C virus (HCV) is rarely observed. Besides liver
tissue, peripheral blood mononuclear cells (PBMCs) could be proven as locations
of HCV persistence. It is assumed that there are further extrahepatic
compartments in the host organism in which virus particles capable of
replication remain, in spite of a seemingly successful therapy. OCCULT HEPATITIS
C: The problem of the existence of small amounts of potentially replicative
viruses becomes apparent even in occult hepatitis C, a constellation in which
anti-HCV antibodies are missing, but HCV RNA in liver tissue and mostly also in
PBMCs exist. CONCLUSION: The precise significance of the HCV persistence in the
host organism is still inconclusive; according to first research results,
however, it can lead to a deterioration of the liver histology. At present, it
is also unclear if patients with occult hepatitis C as well as with evidence of
HCV RNA in the liver and/or extrahepatic compartments after seemingly successful
antiviral treatment are to be regarded as infectious.
If anyone finds it inappropriate to bring context relevant abstracts in these comments, please speak up now.
it is not surprising that therapy can reduce the small amount of virus in occult infection further downwards, but also that there is still no complete eradication.we could take the UND VL that is part of the defintion of the sundrome as a sign that the remaining virus at least does not replicate at any substantial rate. In other words its replication efficiency - if any - is very low, since the residual virus found in the liver is not so ultralow as the plasma virion level. That part is good new and reflects the stability of SVR.
The idea of a distinction between resistant occult virus past SVR vs "nonresistant" as in "primary occult" raises the question RESISTANCE TO WHAT?. the fact that these residuals exist -as now becoming an accepted fact fast- means that they are resistant to eradication for a host of reasons eg that they sit in a liver cell and were able to turn off the antiviral mechanisms inside that very cell, but at price to their fitness nd capacity to reinfect and many more reasons.
But overall the SVR residuals are more likely to carry resistance to further eradication by IFN than the primary occult ones.
The extent to which this lingering HCV presence can cause prolonged liver damage like fibrosis will certainly be studied intensely in the near future and will turn out to be quite different among individual SVRs from nothing to substantial progression. Therefore watching lifestyle, antifibrotic concepts and measures, LFTs and fibrosis extent itself will be quite important. It looks like Echosens will have a bright future.
HCC is another issue that needs to be watched, unfortunately.
Likewise we know that even the "300 000 000 inactive HBV carriers" have an increased rate of HCC compared to non hep controls. Quantitative comparisons of risk cannot easily be drawn, since the two viruses have substantial differences in their oncogenic mechanisms (B has the "x" gene and a double stranded DNA minichromosome (cccDNA), ready to integrate in the liver genome each time a division takes place....
Thus these advanced questions have only a small lit base to support any notions.
Here is another CONTEXT PERTINENT abstract from pubmed (LIKE PUBLIC MED AND NOT COPYRIGHTPROTECTED BUT HERE TO BE USED TO THE BENEFIT OF ANYONE SO VERY MUCH HERE)
Med Klin (Munich). 2006 May 15;101(5):378-83.
[Virus persistence in hepatitis C: lifelong infection despite therapy?]
[Article in German]
Gockel HR, Heidemann J, Lugering N.
Medizinische Klinik, St. Marien-Hospital Hamm, Hamm. ***@****
BACKGROUND: Chronic hepatitis C infection still represents a clinical and
scientific challenge. Exciting progress has been achieved by the use of combined
therapy regimens with pegylated interferon and ribavirin resulting in sustained
virological response rates of 60-80%, depending on the genotype. VIRUS
PERSISTENCE DESPITE SUCCESSFUL THERAPY: Despite favorable longterm data with
regard to viremia, liver histology and serum liver enzymes in treated patients
who comply with the criteria of sustained virological response, a complete
elimination of the hepatitis C virus (HCV) is rarely observed. Besides liver
tissue, peripheral blood mononuclear cells (PBMCs) could be proven as locations
of HCV persistence. It is assumed that there are further extrahepatic
compartments in the host organism in which virus particles capable of
replication remain, in spite of a seemingly successful therapy. OCCULT HEPATITIS
C: The problem of the existence of small amounts of potentially replicative
viruses becomes apparent even in occult hepatitis C, a constellation in which
anti-HCV antibodies are missing, but HCV RNA in liver tissue and mostly also in
PBMCs exist. CONCLUSION: The precise significance of the HCV persistence in the
host organism is still inconclusive; according to first research results,
however, it can lead to a deterioration of the liver histology. At present, it
is also unclear if patients with occult hepatitis C as well as with evidence of
HCV RNA in the liver and/or extrahepatic compartments after seemingly successful
antiviral treatment are to be regarded as infectious.
If anyone finds it inappropriate to bring context relevant abstracts in these comments, please speak up now.
MEDICAL PROFESSIONAL
only to taste the drugs singlular power. Combo trials with no IFN I think are still way out.
With respect to the no IFN/riba cocktails SVR holding power; I hope you are right.
omyst comment also is quite relevant ; We should see the left arm of the distribution curve come out of the fog by now...
The question of "residual disease" is to be seen as a different issue however. Much harder to quantify, since the effects are more insiduous, not like a clean hard VL thats back.
With respect to the no IFN/riba cocktails SVR holding power; I hope you are right.
omyst comment also is quite relevant ; We should see the left arm of the distribution curve come out of the fog by now...
The question of "residual disease" is to be seen as a different issue however. Much harder to quantify, since the effects are more insiduous, not like a clean hard VL thats back.
MEDICAL PROFESSIONAL
the virus was found by in situ hybridization (a method to PCR amplify directly on the tissue mounted on the microscope slides in 3 %of the hepatocytes for the neg strand HCV RNA. This is the Vincente Carreno paper that we have prev discussed. He found overall 19 out of 20 liver biopsy specimens were positive. This whole story is quite incredible, but I found no flaw in his methods whatsoever. All neg controls dead neg.
Thank you for taking your time to answer our questions. I have a question about occult virus.
In the future treatments, will small molecule drugs be able to get to these hidden compartments that large molecule drugs might not get to?
I know a large molecule drug won't penetrate the blood-brain barrier, and most small molecule drugs won't either, but in other areas where it hides, is it known or theorized about things like VX-950, SGP's or ITMN's (when it gets into the clinic) being able to reach those virions too?
TIA.
In the future treatments, will small molecule drugs be able to get to these hidden compartments that large molecule drugs might not get to?
I know a large molecule drug won't penetrate the blood-brain barrier, and most small molecule drugs won't either, but in other areas where it hides, is it known or theorized about things like VX-950, SGP's or ITMN's (when it gets into the clinic) being able to reach those virions too?
TIA.
Thanks for the answer, I guess there is hope in future therapies for this issue.
OK. But didn't you say earlier that certain systems were in place to prevent those virons from breaking through the serum barrier? My understanding is still that SVR (as defined as serum negative six months post tx) is durable 98% after six months and approaches 99% after one year. Other than anecdotal accounts that might be marred by reinfection, faulty testing, etc, -- I don't believe there are any studies to refute the durablity up to ten years. So to me, the question isn't where are they hiding, but if they are indeed hiding can they get out. Studies suggest no.
MEDICAL PROFESSIONAL
Polymerase inhibitors like Valopicitabine should be able to get most anywhere. Protease inhibitors are bigger but still available intracellularly. These drugs dont kill the virus however, only block its replicating machinery. Nevertheless, in the meantime the "natural mechanisms" could get a better handle on these residuals. Again what mostly matters here is the stability of the SVR and that seems to be surprisingly good, as correctly stated above by jim and scott, more surprising now in the light of the new findings.
Have an Answer?
You are reading content posted in the Hepatitis C Community
Learn about this treatable virus.
Getting tested for this viral infection.
3 key steps to getting on treatment.
4 steps to getting on therapy.
What you need to know about Hep C drugs.
How the drugs might affect you.
These tips may up your chances of a cure.
A list of national and international resources and hotlines to help connect you to needed health and medical services.
Herpes sores blister, then burst, scab and heal.
Herpes spreads by oral, vaginal and anal sex.
STIs are the most common cause of genital sores.
Condoms are the most effective way to prevent HIV and STDs.
PrEP is used by people with high risk to prevent HIV infection.
