"There is a huge population of SVRs at this point and if post-SVR persistence were accompanied by measurable health complications it seems likely the data would have surfaced by now. "
That's my take on it as well. If we get good enough technology, we will probably be able one day to detect the presence in our blood of a breakfast cereal we tried once 2 years ago. It doesn't mean our lives are in danger though... we carry all sorts of residues in our bodies, we are living beings. Personally, I think the efforts spent on this sort of research would be better spent working on something that actually helps people with HepC rather than worrying about those who are cured.
tn - thanks for the update. The new Pham/Michalak review appears to have been written before the last couple of papers :
http://www.ncbi.nlm.nih.gov/pubmed/18448695
http://www.ncbi.nlm.nih.gov/pubmed/18220272
refuting RNA detection in PBMCs. The Pham lab is pretty clear that mitogen stimulation is an essential part of the protocol; presumably the increased cell division is required to bring RNA levels to the detectable level:
"In individuals where PBMC were apparently negative for HCV RNA, the use of mitogen cocktails supplemented with interleukin-2 (IL-2) and IL-4 to stimulate T and B lymphocytes and monocytes in 72-h cultures, augments HCV replication in the respective cells leading to enhanced detection of the residing virus[9,13,27]. Using this approach, HCV RNA positive strand could be identified in approximately 75% of seemingly HCV-negative cases[9,13,14,27]. Of note, the presence of HCV RNA positive strand in mitogen-treated cells is nearly always accompanied by that of HCV RNA negative (replicative) strand, indicative of authentic viral replication. "
the Bernardin paper acknowledged this omission but didn't comment further. The Halfon paper, with not unusual Gallic arrogance, ignored the issue altogether. This seems to be at the crux of the puzzle - if other researchers have reservations about this amplification why not just say so rather than ignore the issue? I suspect some of the delays may be technical - the Michalak lab has been studying this topic for a long time and may have perfected techniques other labs can't match yet - not something they'd want to admit.
DD: I believe there are (a few) papers supporting many of the questions you raise post SVR-relapse, elevated enzymes, non-hepatic complications (cryo) and infection through blood donation, if not familial, but they are few in number, particularly relative to the large number of papers supporting improved hepatic outlook from SVR. There is a huge population of SVRs at this point and if post-SVR persistence were accompanied by measurable health complications it seems likely the data would have surfaced by now.
Thanks for asking. I finished tx the end of January, 2005. So, I'm coming up on 3 years SVR.
As far as attributing anything to occult, I'd be hard pressed to say that I can correlate any issues with it. Most of my post-tx stuff I attribute (rightly or wrongly) to the interferon. And I'm pretty well stuck now w/ the post-tx issues I've been carrying since treating. Of the things I can trace to tx'ing, the bigger lingering issues are: lower red and white counts, rosacea-like outbreaks, leftover bone and muscle pain (mostly in the legs), tinnitus (which had kicked in after my first tx in the early 90's and jumped into even higher gear via the peg inf tx in 2004), and my scrambled immune system (which is where many of my biggest concerns lie). I've been researching (with help from HR) some labs that could do interleukin and other cytokine immune testing. Found a few different labs, though no single one of them covers all of the currently available tests. But even with finding these various labs, the real issues become cost and coverage - somehow I (and my doc's office) have to try and convince the insurance company to foot the not-so-cheap tab. (Cue the laugh track now).
One thing that has improved, though, has been the fatigue issue. I had fatigue associated with my Hep C for years, had it in spades through my two tx's, and continued having it for perhaps up to two years post-tx. My bouts these days are much more infrequent and less debilitating. Thank God.
How have things been with you recently? Any changes taking place?
Hope all is well with you and family.
TnHepGuy
By the way, how have you been doing since SVR? Do you notice any lingering symptoms or problems that might either be attributed to the tx drug effects, or possibly the a result of the remaining 'occult' virus? I think that the occult issue might make it hard to differentiate between actual post-tx interferon generated changes, versus post-tx, immune system over-activation issues, if indeed this is how our systems keep the 'occult' viral load under control. How long have you been off treatment now? Have you seen a progression toward feeling better and better? I hope all is well.
DoubleDose
As I have always believed, the resolution of HCV infection, whether by treatment or spontaneous means, seems to generally leave the person harboring a new and different form of the HCV infection. The tag that Pham hangs on it is "Occult" infection, and others might describe it as 'persistent' infection at sub-detectable levels. Pham seems pretty confident that his research is valid, and that it goes deeper than other research articles claiming not to find the virus after SVR.
As he says, the implications of this "occult" virus are the real question, and I continue to wonder about a variety of related issues:
* Can the "occult" form of the virus ever possibly provoke a late relapse under specific or extreme conditions?
* Could the "occult" version of the virus be transmittable to others by blood to blood exchange, or by even more innocuous methods...fluids, etc?
* What are the long term health implications of this low level, apparently 'controlled' virus? Could our immune systems be at risk? Does the virus cause direct damage to nerves, brain, or cell structures in this form?
* Could there be a large, unidentified population out there who now carry "occult" HCV, but have no symptoms, or antibodies to the virus?
* One of the related articles on your occult HCV health pages list mentions "occult" HCV and the possible implications for family members, but does not go further to describe their concerns. You have to wonder whether some sort of sort of close contact transmission might take place with "occult" HCV, that may remain more or less invisible on testing, and invisible when looking at LFT's, etc. Who knows how many people might harbor this controlled form of the virus, without any way to routinely detect it?
As always, these articles are a great basis for questions, future research, and forum debate. I hope my questions (all hypothetical, but largely unanswered) don't provoke the typical round of defensive "attack" responses. I honestly think that Pham and the other Occult researchers are indeed posing either directly or indirectly these same questions in their research conclusions and discussions. I think we all want real answers to all of these questions.
Thanks for your diligence in keeping us all informed of the latest research and insights regarding the behaviors of this enigmatic virus.
DoubleDose
Doesn't appear to have taken very long at all for Pham to post his rebuttal - just as you had thought.
TnHepGuy