New Pham paper re: Occult Hep C

[TnHepGuy_]

Antagonistic expression of hepatitis C virus and alpha interferon in lymphoid cells during persistent occult infection.

"Using paired sera and lymphoid cells collected 1 year apart from 17 individuals with normal liver enzymes for up to 72 months after SVR, it was found that simultaneous activation of lymphocytes and monocytes enhanced identification of silent HCV infection and revealed that in some cases monocytes were the principal immune cell type where HCV persisted. Testing of serial samples further increased detection of occult infection. Ultimately, by combining the above two approaches, all individuals with SVR were found to be silent carriers of HCV."

http://tinyurl.com/yufc93


TnHepGuy

[drofi]

What happens after SVR, when the immunsystem is deeply supressed? Will the "silent" RNA come back to give an active infection?
This has been studied: http://tinyurl.com/2wxv9c

J Am Soc Nephrol. 2003 Aug;14(8):2092-8.
Evidence that clearance of hepatitis C virus RNA after alpha-interferon
therapy in dialysis patients is sustained after renal transplantation.

[DoubleDose]

More interesting information indeed from Willing, as usual!  Thanks for the input, and your comments just reinforce my theroy that the 'persistent' form of the virus after SVR, and 'occult' forms of the virus might just cause as much damage and sx as the full blown virus.  Specifically regarding this reference you quoted:

"Furthemore, HCV-specific T-cell responses are significantly more frequent in occult HCV infection than  in chronic hepatitis C" (from their Discussion section), is also not surprising : that's why infection is these patients is down to the occult level rather than full blown CHC. (your text)

(my comment)
Also, your rationale regarding transmission of the low levels of reproducing virus through saliva, tears, sexual fluids, also corresponds with what I am thinking.  I think these low levels might also prevent a blood borne or 'humoral' antibody response, hence negative on HCV testing.  But what may happen is that the cellular immune responses kick in, produce symptoms, and may be detectable through not readily available HCV cellular immune response testing, as discussed in other linked articles and research.  Here was your comment:

"As  for the infectivity of saliva, tears, sperm, etc. if it works for HBV as a transmission route it's hard to see why it shouldn't also  work for HCV and the low initial titer may effectively prevent the virus from shutting down the immune responses targeted against it."

(my comments below)
I think we are all moving toward a much broader understanding of HCV infection, transmission, 'occult' or invisible infection, and real infection status after SVR, etc.  
My hunch is that this virus may be much more pervasive in society than currently understood, and that there may be 'other modes' of infection, and transmission.  Cure seems to be 'cure', and we have yet to figure out just how small the 'c' might be.  Hopefully the 'persistent infection' after SVR will not lead to even worse immune system problems and extra-hepatic sx for many or most of us.

The other very unrecognized issue is: how many people out there have become infected with a 'dormant' or low level cellular (currently undetectable) version of the virus, and what are the implications as far as:  1. transmissability.  2. long term health consequences, and impact on immune system, and direct impact on cell structures. and, 3. Could some of these 'dormant' or invisible infections convert into full blown chronic active HCV blood/liver infections, and how?

Food for Thought on a rainy day!

DoubleDose  

[willing]

Re Quiroga'06 I tend to see this as evidence that supports the view that there's nothing special about occult virions, there's just less of them. Patients with occult virus generated HCV-specific CD4+ and CD8+ T cells in much the same way as those who spontaneously resolve acute infection.

"Furthemore, HCV-specific T-cell responses are significantly more frequent in occult HCV infection than  in chronic hepatitis C" (from their Discussion section), is also not surprising : that's why infection is these patients is down to the occult level rather than full blown CHC.

Overall, it seems unlikely that the virus'  small, 9600 nucleotide, genome leaves enough room to encode significantly different personalities (eg "blanks"). Apart, from the minor systematic variations described above, including genotypes differences, I think there's basically a single HCV molecular machine and reproductive pathway. The recent San Francisco truncated genome study doesn't contradict this - just shows that the machine need not be encoded in every viral copy.

The crux of the puzzle seems to lie in exactly how HCV disrupts the CD4+/CD8+ response - sort of like al-quaida planting operatives at the NSA.  My hunch is that whether SOC works or not hinges mostly on whether that huge, year-long, wave of synthetic ifn is sufficient to remove the agents of that disruption.

I don't have access to the ultra-centrifugation paper but the abstract looks promising: if you're looking for something scarce, concentrate it before measuring. Techniques like this that make "occult" virus easier to measure should remove some of the exotic mystique associated with its current only-detected-in-research-lab  status. As for the infectivity of saliva, tears, sperm, etc. if it works for HBV as a transmission route it's hard to see why it shouldn't also  work for HCV and the low initial titer may effectively prevent the virus from shutting down the immune responses targeted against it.

[DoubleDose]

Thanks for your additional comments and references.  In the Occult article that you linked, look closely at the last sentence as copied below:


"These findings demonstrate that HCV-specific cellular immune responses are markers not only of previous exposure to and recovery from HCV but also of ongoing occult HCV infection. "


Very interesting comment, in light of the fact that one of the coming studies, by a well known hepatologist,  will supposedly look for cellular immune responses in various cells and tissues of close contacts and intimate partners to those infected with or previously infected with HCV.  If they find these HCV specific 'cellular immune responses' (as I will predict they will), it then would also seem to indicate ongoing 'occult' type infection in those persons. (according to the researchers statement above).

That plays right back to the comment that you made, about the 'occult' form of the virus potentially being in the entire population (to some degree I would think).

This would be pretty major information, and IF the occult virus proves to be 'pathological' in some way, then we have a global health issue confronting us.  The real key will be to determine if this 'occult' form, (or forms) of the HCV virus can be transmitted in more casual ways, as in fluids, etc., and does it then generate detectable cellular immune responses. (as in fluid exchange, etc)


Although a precedent for more or less universal infection already exists for several viruses, like Herpes Simplex, and Human Pappiloma Virus....this might be a lot less benign, and might be at the root of at least a few medical conditions that seem to be on the rise in the past 40 years or so. It might also validate my conjecture that the very high HCV rate of infection in alcoholics DOES have a rational explanation.  The alcohol may allow the virus to overcome the immune system barriers that would exist in normal persons.  It might also 'potentiate' the abilities of the virus, thus aiding it in crossing immune system control.

I am jumping ahead on this, but these are lines of reasoning that I have been following for quite awhile now.

Good to hear form you.  I hope you are doing well.

DoubleDose

[jmjm530]

I spoke to one manufacturer, Nature's Plus, that has gotten some good reviews -- and they stated that their Red Yeast Product is still using the original formulation and they do not intend to change it since it doesn't contain Lovastatin. This appears then to contradict the article that states Red Yeast Rice is ineffective without Lovastatin.

What brand of Red Yeast Rice did you take and what daily dose? That's very good news that it's working well with your normal diet. I found the same thing with Lipitor so far.

Regards,

-- Jim

[TnHepGuy_]

willing - many thanks for posting your analysis and insights. As to your points:

1.) It is potentially troubling news for the blood supply. Which would then bring on the question: if occult is passed on in this manner, what does it do in the newly-infected's body? become acute and/or chronic Hep C? stay at an occult level? and if so (occult level), would this be more-or-less in vivo proof that it truly is a different type of infection? Other questions along similar lines would then be: (ala DD) is it transmissible via other ways/fluids? If so, might then occult Hep C (and how many other 'occult' viruses?) be virtually throughout the entire human populous?

2.) SVR certainly does seem to 'hold up' in the face of occult - with all of it's very desirable benefits. Your thoughts on non-SVR-related therapies are similar to things I have thought of in the past - ways to minimize viral impact for those who don't/can't make SVR the 'traditional' route.

3.) Thanks for pointing out the 'viral niche adaptation'.

4.) Also in terms of occult detection, here are a couple of recent papers:

Serum IgG Antibodies to the GOR Autoepitope are Present in Occult Hepatitis C Virus (HCV) Infection Despite Lack of HCV-specific Antibodies.

http://tinyurl.com/27w94w


Ultracentrifugation of serum samples allows detection of hepatitis C virus RNA in patients with occult hepatitis C.

http://tinyurl.com/ypzfut

5.) I think it's still very early in the research game and the news of occult's potentially chronic effects will begin to be revealed slowly over time. As far as I'm concerned, the increase/difference in HCC rates in SVR's is enough bad news in-and-of-itself for SVR's and non-SVR's to remain vigilant in ongoing testing and continued information gathering.


Also, did you happen to see the paper referenced above?:

Cellular Immune Responses Associated with Occult Hepatitis C Virus Infection of the Liver.

http://jvi.asm.org/cgi/content/abstract/80/22/10972


Jim - thanks for posting the article. I hadn't seen or heard of that. Nice to know that the FDA has wiped the slate clean of the original beneficial, 'natural' ingredient right out of the Red Yeast Rice, eh?

I'm not taking any statin. I've strictly been on the Red Yeast Rice. My most recent labs were right in line with my previous ones showing the initial drop. I take these latest results as even better news since before the first round of testing I was fasting (for weeks) without meat, dairy and olive oil, whereas for the most recent one none of those were avoided prior to testing.

I may have to make a phone call to the manufacturer of the Red Yeast Rice that I take to see what they have to say.


DD - I always enjoy your thoughts, insights and take on things. Thanks for continuing to post.


TnHepGuy

[willing]

Jim: well, as memory serves, I believe you did in fact cite the illustrious Dr.Neumann as an expert witness a  while back..but no, can't say my flattery skills have brought me much success to date. Maybe it's the hair?

DD: thanks for the comments. I share your interest into this question of whether low-level viral presence is just natural background biological noise, like barnacles on a ship hull, or whether it always represents a pathology. One item I noticed in this last round of reading is that Tomasz I. Michalak  is a key investigator in this area. Pham is actually a post-doc in his lab at St. John's and a couple of other papers we've discussed here including the HBVHCV connection came out of his lab. One of the references in Pham'07 is to

Occult persistence and lymphotropism of hepadnaviral infection: insights from the woodchuck viral hepatitis model.
Immunol Rev. 2000 Apr;174:98-111. Review.
PMID: 10807510 [PubMed - indexed for MEDLINE]

haven't gone through this yet, but it seems to set out some his thoughts on how viral intrusion into the immune system is then used to manipulate the response away from viral detection and destruction. BTW, as far as "total eradication" goes, I would bet that the new HCV-targeted drugs are more likely to succeed than the "natural", ifn-based ones.

[jmjm530]

DD: " I always wonder why so many of us experience a feeling of almost total 'cure' for a few weeks to a months or two right after tx ends...  In general, I felt WONDERFUL for a period of time...then it all went back to the familiar sx! ..."
------------------------------------------
I also felt pretty good the weeks/first month of so, coming off the drugs, but I wonder if it could have more to do with the release of toxins (tx drugs) as opposed to anything viral.

Maybe not the best analogy, but I remember when I stopped smoking -- and I think anyone who stopped smoking can relate -- the energy/euphoria you feel for a very short period of time until the nicotine withdrawal kicks in.

All of a sudden you don't feel so hot and that transitional period can last quite some time. Eventually, the nicotine starts leaving your body and you end up feeling more or less the way you did before you started smoking.

My doc called the transitional period "interferon hangover" and said it might last six months or so, but no doubt it varies considerably. Beyond that,  from what I've read here, many report feeling better than they did pre-treatment, many report feeling worse, and many (including myself) report feeling about the same. Well, at least the same physically, but like some others, I feel treatment has taken something from my spirit that eventually I hope to get back. My theory is that for some of us  it's akin to post traumatic stress syndrome, and the stress is the treatment.

-- Jim

[DoubleDose]

Thanks very much for your follow up and thoughtful, insightful commentary.  I think the information and studies cited leave little doubt that the virus remains after SVR, reproducing, yet 'contained' by a now more competent immune system.  This is much as I have been envisioning the SVR process, and still fits nicely into my theory that some people may just 'carry' the virus, with no overt signs of infection.  I do believe that there can be this low level, post-SVR-like infection within some individuals who have never had the chronic active version of the virus.  I now see clearly why it is chiefly the blood transfusion cases, and IVDU's that show up on the HCV chronic infection radar screen.  Their immune response was 'overwhelmed' by the introduction of high viral counts of HCV DIRECTLY into the bloodstream!  Thus triggering the common, and well understood form of the infection.  This other form, low level persistent virus, may just be a common viral state for HCV, and may be held perpetually in-check in those who have it in their systems...unless something rare, and major occurs, thus allowing the in-check infection to cascade into the blood, overpowering the immune system.

Still just my theory, but it might ultimately end up explaining much of the mysterious problems out there like: CFS, ME, fibromyalgia, various forms of IBS, depression, etc.  Remember, many of the researchers (if not most) are almost insistent that there is some sort of undiscovered 'viral cause' to many of these ailments, but have not yet been able to isolate the offending virus. (Why NOT HCV?)  Recent research on depression has brought a number of studies pointing ot a viral cause as well.  Lots of other burgeoning health problems today in our society, that are unexplained solely by the environmental conditions, etc.  Remember, we have tightened up many environmental, chemical, and pollution standards greatly from what they were 30 to 60 years ago, yet the population seems worse off today, and the young in our society are beginning to be heavily impacted.

I also continue to believe that there will be more to the persistent virus story than we currently have read.  Just because they have not yet identified long term consequences of this lingering virus, or other ways it may be impairing our brains, nervous systems, etc....does not mean that none of these things are indeed happening.  In looking at the ongoing health and symptoms of the SVR population, it is obvious something is happening to many of this group.  Either the interferon is the culprit, on a long term basis, or the virus continues to provoke the many 'extra-hepatic' sysmptom that we are familiar with (either through immune system foul-up, or directly), OR the virus just damaged us so much before treatment, that we will never improve or fully recover (which I doubt is the real reason).

These are my thoughts.  I still also believe there may be a different mode of transmission possible with either the persistent HCV virus, or even the normal active chronic virus...that is:  a transmission that enters either through fluids, or other close contact, which is never powerful enough to provoke a typical blood infection.  It may be a sexual exchange, salivary, or other cellular exchange, but ultimately I believe the virus could find a home, reproduce in these fluids, and remain contained just as the SVR's seem to experience.  Ongoing research with family members and close contacts will further clarify what and if something of this sort is taking place.  Newer, more highly amplified tests, and testing of other cells and fluids will also indicate whether there is an alternate, more benign, form of the HCV infection at play.

As much as I HATE the concept of HCV living on in our bodies after SVR, and would rather pretend that it does not happen, I am fully persuaded by the mass of research that it is indeed a reality...and merits lots of study...to understand the ramifications and long term consequences...as well as to understand how to best deal with this version of the virus in the distant future (medically speaking).
It certainly can't be very good for us, to have this ongoing infection in our systems.  At least that is my belief.

Great to hear from you, and thanks again for your highly precise and rational analysis.  I wish the doctors could look at the available information and do the same!

DoubleDose

PS One other thought:  I always wonder why so many of us experience a feeling of almost total 'cure' for a few weeks to a months or two right after tx ends.  I know I felt FAR better for those three to five weeks than ever before or after tx and SVR!  Almost as if the virus were really knocked out completely throughout the body (for a short while!), and everything could work properly.  My ED vanished for a month, I felt very energetic and NO brain fog, etc!  In general, I felt WONDERFUL for a period of time...then it all went back to the familiar sx!  Could this be the reassertion of the persistent virus, after it was almost knocked out of existence?  Could there have been a short window of real 'eradication and cure'....Who else has experienced this feeling after tx?????   A very strange phenomenon.

[mikesimon]

I agree completely with your analysis. Thanks for the taking the time to elucidate this very complex issue. Mike

[jmjm530]

Don't know if you've seen this regarding Red Yeast"
http://heartdisease.about.com/b/a/254767.htm?nl=1
-------------
As I mentioned last time, I've been on Lipitor 100mg with good results. However, it appears that I've been experiencing some fatigue -- and *possible* minor muscle issue -- so my plan is to stop the Lipitor for a few weeks and see how I feel. If I feel the same (conclusion: Lipitor isn't causing those sfx) then I'll go back. If I feel better, then the plan was to try Red Yeast Rice Extract or possibly a yeast-derived statin (Lipitor is synethic) like Lovastatin. Then I read this article and realize that the Red Yeast landscape may not be as simple as I thought.

Could you please post again which brand of  statin you're taking and in what amounts? Also, have you had any recent cholesterol labs? The article seems to suggest that: (1) Red Yeast without Lovastatin may not work; and (2) Whatever Red Yeast Products that still have Lovastatin may be pulled from the shelves soon.

I guess the proof will be in the pudding, or in this case how the pudding affects your cholesterol.

All the best,

-- Jim

[jmjm530]

Willing: As to the threat represented by presence of low-level virus, the evidence to date seems to side more with Jim’s, Alfred. E. Neumman ‘what me worry” viewpoint than with DD’s.
----------------------------
My, you have a way with compliments. Bet you do real well with the women :)
Hope all is well.

-- Jim

[willing]

Finally got a little time to read the new Pham paper tn posted. I’ve  been mulling it over and, since I met with my large-caliber hepatologist last week, wondering what practical implications this might have. Some comments on the changing landscape below, I’d be curious to hear any thoughts  on other ways to read the tea-leaves.

1) much research has been published since the early, somewhat panicky, discovery that virus appeared to live on post SVR. Labs in Canada (Pham,Michalak), USA/Poland (Radkowski), Germany(Fitytili, Kretzschmar), Spain (Castillo) and Cuba (can’t remember authors) have independently and reproducibly confirmed that virus exists in individuals found serum-UND by conventional commercial tests. This is no longer  news. The source of infection in  Kretzschmar’07 was a newly infected donor, not an SVR , but this is irrelevant to the  failure  of commercial tests to detect the infection While this is somewhat troubling for us, it’s really bad news for those in charge of monitoring the blood supply.

2) SVR is as desirable as ever, but the point of SVR is not elimination of the virus but “fixing” our immune response to its presence, that is, to renegotiate the terms of coexistence. It’s starting to look as if most patients never fully eradicate the virus.  The positivity index in the last column of Table 2 of Pham’07 is a solid ‘+’, 100% of patients turned up virus at some point during the various follow-up serum and PBMC blood draws.  On the other hand, SVR is durable and consistent, all of these patients also remained  SVR on all of their standard, commercial, serum follow up tests.

If the end-benefit of IFN based therapy is merely to train the immune response to quit botching the job and eliminate the endless round of infection among liver cells which leads to fibrosis (and ultimately hcc)  alternative strategies that simply reduce viral efficacy (I’m thinking maintenance alinia/statins) might achieve the same end lifetime benefit as the SOC ordeal.

3) A couple of  the technical details in Pham’07 are particularly interesting. Anyone who believes the post SVR virions are “blanks” should study their Fig 2. which gives the results of sequencing  the obtained RNA relative to a known HCV standard. There is near perfect agreement and the variations/polymorphism  present occur at very specific points and are consistent, draw-to-draw. They point out that this suggests adaptation of the virus to a niche environment (eg PBMC cells). Frustratingly, I don’t think anyone has yet cloned all of the sequence of  an occult virion, so this evidence is still preliminary.

4) The most interesting evidence in their paper IMHO, is shown in  Fig 4. Their lab and others have previously shown that a good way of facilitating detection of HCV RNA in PBMCs is to stimulate the cells with mitogens. I’m not sure the mechanism is understood yet, but it’s along the lines of giving the PBMC  a double cappuccino – the cell does more of everything including virus production.  Part of their focus was developing production-level tests for occult RNA detection.

However….when they applied their mitogen cocktails (C5 and C5L)  to cells that *already*  had high RNA counts, the cells’ production of IFN increased *and* viral RNA was either significantly decreased or eliminated completely. The implication here is that cells will tolerate a certain low level of HCV RNA but are competent to eliminate the virus if the “balance of coexistence” is tipped in the virus’ favor.

5) As to the threat represented by presence of low-level virus, the evidence to date seems to side more with Jim’s, Alfred. E. Neumman ‘what me worry” viewpoint than with DD’s. For sure there is some evidence that the virus is up to no good : (a) Fityli’07 noted that one of the SVR’s in whom they detected low-level HCV had persistently elevated ALTs,  (b) in that cryo detection study from a while back (can’t remember cite) there was a clear correlation between cryo and post SVR PBMC HCV (c) pham ’07 includes the comment “liver biopsies from these individuals [ SVRs with low-level HCV] occasionally reveal histological evidence of protracted minor inflammation, frequently mild-to-moderate fibrosis or, in rare cases, even active chronic hepatitis” (d) there is that disturbingly small difference in SVR and non-SVR HCC rates. However in balance, this still looks like minor damage. There may be more bad news in the pipeline, but it hasn’t surfaced so far.

References:
Kretzschmar ’07 : First case of hepatitis C virus transmission by a red blood cell concentrate after introduction of nucleic acid amplification technique screening in Germany: a comparative study with various assays.
Vox Sang. 2007 May;92(4):297-301.  
Fytili’07: Frequency of very low HCV viremia detected by a highly sensitive HCV-RNA assay.
J Clin Virol. 2007 Aug;39(4):308-11. Epub 2007 Jul 12.
Pham’07: Antagonistic expression of hepatitis C virus and alpha interferon in lymphoid cells during persistent occult infection.
J Viral Hepat. 2007 Aug;14(8):537-48.

[DoubleDose]

I agree completely regarding the autoimmune theory.  I do believe that either the virus, or the treatment, or both together, cause lots of autoimmunity, which in turn causes lots of nasty symptoms.  My major concern with the 'persistent virus' possibility (or probability) is that by just being there it keeps the autoimmune responses going long term, and keeps us feeling like we are still on treatment in many cases.  I think the autoimmune issue is the central cause of our wide range of symptoms, before, during and after tx.  Arthritic problems, joint pain, skin manifestations, fatigue, sjogrens syndrome, diabetes, etc. etc.  Reads like a Lupus symptom sheet.

I think that if the virus were totally, completely eradicated after tx we would have a lot less ongoing symptoms (even less interferon hangover), and also after a few years we would lose the antibodies to HCV that mark us as HCV infected persons, even though SVR.  A very few people seem to lose the antibodies, and maybe they are the fully cured 10% to 15%.  The rest seem to keep the antibodies for life, or so it appears at this point.

This is chiefly why I think the 'persistent viral issue' is still pretty important, and will need to be addressed down the road.  I think the SVR and 'cure' are great, but that a CURE would be even greater!

DD

[pigeonca]

I meant "and so on..."  

Nothing's gonna be soon, I'm afraid, except maybe a rise in Vertex's stock price following just enough of a drop to make a purchase worthwhile. But if all of the stuff in this thread turns out to be true, that our brains and nervous systems are slowly turning to pudding, then I hope the pharma companies are working on meds that will eradicate ALL the virus - soon.

[pigeonca]

As one who suffers from autoimmune problems, which began before diagnosis and have somewhat - but not entirely - resolved after 6 months of UND, let me speculate that these virus fragments, bullet shells, whatever you want to call them, radically amp up the immune system - and that it's this over-secretion of one's own interferon, etc. that causes sides to persist after SVR.  If these fragments disappeared entirely, perhaps the immune system would calm down and return to normal levels.  

I'm starting to believe that everything (well, maybe not everything, but lots of things) is the result of autoimmunity.  Supposedly inflammation causes half of mankind's ills - isn't inflammation sort of an autoimmune reaction?  And soon...

[desrt]

Makes me want to go right out and get a biopsy of my spinal fluid.
Not.

If I could co-exist with the virus (probably) for decades I can probably stick it out for a few more years with some +/- strand RNA frags floating around in my compartmentalized systems. Whether or not I'm one of the lucky 10-15% who are totally undetectable everywhere in my body is a matter of only academic interest.
The idea that occult HCV is somehow communicable is within the realm of possibility, but I believe in the concept of 'Least Hypothesis' - the simplest explanation is usually the true one. It seems much more likely to me that clusters of people with 'chronic fatigue' type symptoms or metabolic syndrome are more easily explained by our increasingly polluted environment or a shared cr@ppy diet than an infection that doesn't fit any known pattern of epidemiology.
As for occult infection causing post-tx physical complaints similar to some people's pre-treatment symptoms, what about those of us who were asymptomatic pre-tx and only developed these problems after treatment? Again, Occam's Razor says it's the treatment, not the virus.

[DoubleDose]

Pigeon:  The fibrosis SOMETIMES reverses, or sometimes gets no worse (sometimes gets worse also), because the active, out of control infection has been quelched, and now has become only a low level, 'immune system controlled' viral infection.  The fibrosis can improve, but it appears the infection remains, at some level.  Can this low level, persistent virus, that the researchers keep finding, cause any serious harm, long term?  There are no real answers to this question yet.

Beamish:  I wouldn't worry at all.  SVR is still SVR, and the low level infection seems to be permanently under control by the immune system, barring some really calamatous event, like the immune system shutting down, etc.  So far, persistent virus does not equal relapse.  It is a different  mode of infection, and seems to not provoke relapse.  It may ALLOW for relapse though, in some rare very and unique cases, potentially.  

Pigeon:  I do not doubt the benefits of SVR at all, and of course fibrosis reversal, or lack of progression are good things brought on by SVR...I am only concerned that the persistent virus may be doing OTHER things, sort of under the radar, and may have an impact on our nervous system, brain, and immune system function....as well as the obvious concern that the researchers voice: a POTENTIAL source of viral reactivation, or transmission through blood exchange.  Still lots of unknowns here, and much more study needed.

DoubleDose

[beamishboy]

i am testing next month for 1 year post trx...now y'all got me worried,again...How long o lord ,how long?...heck SVR with a few cooties gonna have to work...what's the alternative?
thanks for the updates tho...i would much rather know the latest  research findings then depend on doc..this site is CUTTING EDGE!!!!!

[pigeonca]

If the cooties are replicating in various bodily compartments, including the liver, why do some SVR's experience reversal of fibrosis?

[DoubleDose]

I also am not very confident in the 'blank bullet' explanations because there is no proof that they are truly blank.  I know of no studies to determine infectivity of this material.

The 'tropism' issue you referred to is also of interest.  If HCV is T-Cell tropic, Lympho-trophic, saliotropic, bone-marrow tropic....what else might be at risk from an infection standpoint?  We really don't know.  Brain cells?  CNS cells?  Who really knows.  And as far as 'tropic' goes, I do not know why the virus would have a strong propensity (tropism) for these other areas, yet not be reproducing?  How does that make sense?  Many, many unanswered questions.  

This subject also touches on the thread on alcoholism and HCV from several weeks ago, in which I have postulated that the virus just might be 'latent' or 'silent' in many people, and alcohol abuse, and extreme binge drinking may just 'activate' the virus, to a detectable, blood/liver, chronic infection.  Possibly an explanation for the much higher HCV rate in alcoholic (non-IVDU) populations.  A truly little understood subject.

[DoubleDose]

Another comment is that: researchers have not yet proven that the persistent virus is able to be transmitted to others and cause infection....but what if it transmits to others in the same mode that it exists in SVR's...that is, basically undetectable and at very low levels within specific cells and organs.  Only extreme amplification would show these infections, just as is needed with SVR's....

This gets more to my theory that HCV may be transmitted in 'silent' or undetected modes, rather than only as an active blood/liver infection.  Maybe a sort of low level, 'in-check' infection.  As one of the studies above noted about occult HCV...only the cellular immune responses tip one off to the fact that there is an underlying HCV infection.  No blood antibodies, and no HCV load on PCR testing....

One prominent HCV doctor is conducting a study on just this subject, to determine whether there are HCV cellular immune responses in close contacts of those infected with HCV.  The next step, if he finds a positive pattern, would then be to look for low-level replicating virus within those close contacts.  In otherwords, a 'silent' or 'invisible' HCV infection, not previously known to exist.

DoubleDose

[DoubleDose]

Once again, I think this persistent infection after SVR, as it is being described, and frequently detailed and validated by researchers, just MAY be one of the major reasons why so many SVR's never feel fully recovered, or 'well'.  It is not uncommon to find very high percentages of SVR's with the same complaints they had when they were HCV detectable, before their 'cures' were achieved.

It seems that the medical community is not very interested in finding out why these replicating viruses remain after SVR, and even less interested in any symptoms you might have after your 'cure'.  Its a real shame, because until the real facts are looked at squarely, and acknowledged, we won't have more than a partial 'cure' with a very small 'c'.

I hear people say that: it can't be true, shouldn't be true, is too terrible to contemplate, the HCV docs all say it is not true, etc. etc.  Meanwhile the researchers keep finding more and more evidence of ongoing infection, and everybody just keeps sticking their heads in the sand.  Personally, I am not sure that the SVR really does much more than remove most of the active virus from its chronic, high intensity replication in the liver and blood.  I think the lingering replicating virus may persist throughout the body, and cause problems in the brain, CNS, lymphatic system, and to a smaller extent the liver, and blood.  I think we may still be symptomatic after SVR (in many cases) chiefly because the 'infection' is still at work in our bodies.  Who says it has to be at ultra high levels for it to cause any problems?  I have not seen those studies.  Nor have I seen ANY studies refuting the persistent virus found after SVR by an increasingly larger number of researchers every year!

Wishful thinking is one thing, but evidence, fact, and study after study carry a bit more weight.

DoubleDose

[Whrose]

i have been following this research also and it has been a topic that chills my very SVR bones.
from my understanding, negative sense viral strands are not infectious and must be transcribed by positive sense RNA by a RNA polymerase.  whereas a positive sense viral strands are identical to viral mRNA and can be immediately translated by the host cell, directly cause infection but may be less infectious than the whole virus particle.
research has proven hcv tropism in PBMC(monocytes and macrophages), WBC, Dentritic cells,T-cells,B-cells, and bone marrow. but from what i read hcv is unable to replicate in these cells...but that is a theory and who knows...at this point.
by these articles it would appear that they are finding negative and positive sense virus in PBMC and  the liver in people with SVR.  i took all this to my doc and he told me this " these are blank bullets and not capable of causing hepatitis"  personally i never quite felt confident in his explanation.
from what i read researchers are not sure what this means and further study is indicated. but i have 'mine eyes wide open' for more information like this to come. thanks for posting.
a very fascinating topic!