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Cell to Cell transfer of hec-c
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Cell to Cell transfer of hec-c

I am really surprised that know one responed to my earlier post.  This research paper explains more about why some people handle the virus and others don't and most important why viral load means nothen. With cell to cell transfer there is no way that TX is going to work.  I suggest you all read this. It explains why the virus moves so slow in most and can replicate so fast in others. As I always thought and the numbers bear me out,  you are more likely to die with the virus than because of it.  Sure its causing damage slowly but for the most part if you don't have cell to cell transference your bodies own imune system will keep it at bay.  There is a lot we still don't know about this virus and it bothers me some to see the fear factor so high that some jump into treatment with the chance of doing more harm than good.  
                                                                                                                                        Ron
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Avatar_f_tn
i was one to jump into treatment, and VERY glad i had the option to do so... My biggest fear was  my children getting this from me, and therfor the #1 reason why i treated with no liver damage. And from what I understand the sooner one treats the better the odds are of clearing.. (The less damage one has the better chance at SVR?) Please correct me if I am wrong
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Avatar_m_tn
You kinda miss my point.  This has to do more with cell to cell transmission and the fact that interferon won't work on this.  As far as not giving it to your children I would still be very carefull.  I am not a believer of that.  Ask your doctor if he would be willing to take a blood transfusion from you.  See if you can now donate blood.  

                                                                                                                                        Ron
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Avatar_n_tn
after a quick review of the article. i think the point it was making why it is hard for the adaptive immune systme to form effective antibodies. also one of the reasons it has been difficult for researchers to develop an effective vaccine. however the innate or cellular immune response is still fighting the virons considering this is operating effectively.
i am not sure how you concluded SOC will not work based on this article and cell to cell transfer?
best regards
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Avatar_m_tn
It plainly states that antibodies can only attack outside the cell.  If the transference is between cells then bosting the imune system with TX will do nothen.

                                                                                                                                          Ron
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Avatar_m_tn
Viruses generally enter a cell, replicate themselves, and burst out of the cell with large numbers of copies to infect another cell in the same manner.

However, some viruses can move directly between cells. "Cell to cell transmission" allows them to bypass some of the body's most potent defence systems as antibodies can only attack outside the cell.

Scientists have so far believed that the Hepatitis C virus does not have the ability to move directly between cells, but this has been disproved by the latest study that involved liver tumour cells infected with the virus.

This is big news and at least for me answers questions I have had for a long time.

                                                                                                                                     Ron
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Avatar_n_tn
Do you have the link to the original full article?  I saw your post, and the copied portion of the article that you provided in the post, but no link.  I would like to review it, to see if any of the findings tie into the "HCV persistence after SVR" issues, or the possibility of non-blood transmission, from one cell system to another person's cell system (salivary, sexual, gastric, mucous membrane, etc).  If there is no antibody response to such an infection or transfer of the virus, then the researcher's findings might support some of my more 'radical' ideas about how the virus may operate.  I still strongly suspect a non-blood based, atypical form of transmission between close contacts, intimate partners, and possibly family members...based on a cellular transfer, and non-antibody provoking localized, or compartmentalized infection which is initiated, and maintained by the inewly infected person, but not converted into a full blown HCV blood/liver infection.

If you have more info. on this article, and a link, I would enjoy reviewing it.

DoubleDose
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Avatar_m_tn
This is all I have   http://news.bbc.co.uk/2/hi/health/7075569.stm     I don't think people really grasp what the research says.  It goes a long ways to explain why some people have rapid progression while others can go decades.

                                                                                                                                        Ron
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Avatar_dr_m_tn
My analysis of this discovery is as follows: I hope many people will try to absorb at least some of the content, since a throrough understanding  of the anti HCV immune mechanisms actually at work and knowledge how the virus spreads has, in rare cases- sometimes therapy deciding relevance.

Direct cell to cell transfer refers to an alternate mode by which the infection can spread from one  hepatocyte in the liver to another ( its neighbor in the hepatocyte columns that is the central structural element in liver histology).
The normal mode is to release – not by bursting, but by an exocytotic mechanism that does not kill the infected cell mature HCV virions into the sinusoids ( the bloodstream) where they circulate and then finally after having circulated for a while and returning to the liver, infect another, available hepatocyte by attaching to one or several not well characterized receptors on the sinusiodal surface of that hepatocyte, been translocated through its cell membrane and starting the intracellular life of HCV , now in a new host cell.  While circulating, some of the available antibodies, reactive to virion surface B-cell epitopes,  will bind  with HCV surface antigens, and will therefore to some degree attach to the circulating HCV virions, but typically not well enough to neutralize the virus (by blocking it from binding to a new host hepatocyte).
The virus manages this extremely critical  “escape from neutralizing antibody” feature by having evolved such a surface coat of proteins that it has enough lipophilic amino acid residues placed at strategic points as to bind circulating lipids, that give it a secondary, soft coat, that prevents the antibodies to reach the epitopes and hence effective, strong binding.
It is for those reasons, that up to now, no effective vaccine has been found against HCV and also that immune globulin preparations from hyperimmune, acutely HCV clearing individuals, used as donors, to prepare  “HCIG” in analogy to”HBIG” – a highly effective antibody preparation against a limited number of HBV virions, ARE ONLY WEAKLY EFFECTIVE to prevent de novo infection of hepatocytes by neutralizing antibodies , as is highly desirable in the transplant setting and as is routinely practiced in the transplantation of HBV patients.

This lengthy explanation was given to first clarify the point, that humoral immunity – the production of antibodies by virus epitope specific B cells - plays only a minor role in the overall immune defense mechanisms against HCV, with or without Interferon.

Innogenetics in Belgium as well as an Israeli company is currently working  on the development of two strongly binding human monoclonal antibodies against HCV surface epitopes in the hope to make some contribution to the prevention of post transplant HCV reinfection. They are also working on the development of a therapeutic vaccine against HCV, using a string of T-cell epitopes. When I asked their chief scientist – indeed a god friend of mine through past collaborations, if they also intend to use the monoclonal as an adjunct in chronic HCV therapy, his answer was flatly  “ We are not going to burn us out in the “chronics treatment market.,  Transplantation reinfection prevention is a realistic goal”.

I hope that it is now understood that the role of antibodies in HCV defense is very limited. The language used in the BBC article is not scientifically sound.

The immune defense against HCV is firstly by adaptive T-cell  immune responses

such that cytotoxic Tcells, presented and  primed by dendritic cells processing phagycytosed virions (into class 1 peptide fragments of 10 amino acids, called class 1 epitopes)  primarily in the lymph systems of the body

and inside these lymphnodes further primed and instructed by helper T-cells, that itself get primed by larger fragment epitopes – so called class 2 epitopes, that are derived from the proteolytic processing of the virions in the bodywide innate immune cells  (dendritic cells, monocytes) and after this

those cytotoxic T cells now specifically primed to HCV specific peptide fragments go looking for cells/hepatocytes  that show/ “present” such HCV epitopes on their outside cellular surface bound onto the surface groove of class I MHC proteins.

If found ( molecularly recognized by proper tight fit) these cytotoxic T cells will not kill the infected hepatocytes by either drilling a large hole in its outer cell membrane ( the perforin pathway) or engage the Fas/Fas ligand interaction which instructs the hepatocyte to kill itself. In this way, one HCV production factory is permanently eliminated.
Furthermore as an additional, sometimes even more important mechanism those activated cytotoxic T cells , upon engagement of their T-cell receptor with the fitting MHCpresenting HCV peptide will release local gamma Interferon and other cytokines, that in turn will reach, by diffusion,  hundreds of cells in the immediate vicinity of the specifically recognized hepatocyte.
This will, via surface receptors, intiate a strong activation of the antiviral mechanisms inside those hepatocytes, sometimes strong enough to eliminate the virus, that is currently sitting in its bowels, happily replicating.

In concert with that, the older nonadaptive, innate immune response, inside the hepatocyte itself  and in the numerous immune cells present in the liver, like Kupfer cells, Macrophages, NK and NKT cells, even the endothelial cells lining the hepatic capillaries “sinusoids” are at work to generate a local cytokine milieu that is principally antiviral in its  effects, albeit with limited efficacy, causing the infection to be chronic, with an ever ongoing battle between those clearing forces and the wildly replicating HCV inside the infected cells.

The new aspect of the article from BBC is, that infection of a previously uninfected hepatocyte can occur not only from the sinusoid/ Disse space ( the bloodstream) by also by direct crossing through a double cell membrane, separating it from its neighbor – the short route. This aggrevates the situation insofar as the spread of infection through this shortcut will speed the dynamics of viral propagation and ensures  ( for the virus) that even if you were in theory to remove all virions from the bloodstream, by filter, ozone, silver??, methylenblue or strongly binding monoclonals, that is to reduce your viral load to ZERO by extrahepatic means, the infection would still spread through this secondary intrahepatic route.

BUT since such extrahepatic removal plays only a minor role anyway in the actually effective armamentarium of the IFN superprimed immune system in combo with riba it is wrong to state that this discovery explains why SOC often does not work well.
It has no direct application to therapeutic considerations other than to further discourage efforts to block viral entry or neutralization of HCV in the circulation. The actual extent – that is how frequently this transfer mechanism is actually at work in the in vivo human HCV population – remains to be determined.

DD : No new pathways on how the virus will be transmitted from human to human are envisioned or follow logically by this discovery.

We furthermore know that the same lateral direct hepatocyte to hepatocyte transmission is in existence in HBV infection, but also that its contribution to viral spread seems to be minor.








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Avatar_m_tn
Thanks for your take.  It explains some aspects but leaves other unanswered.  I keep going back to the 15% who are able to defeat the virus on their own. It has to be the anti bodies and the lack of cell to cell transmission.  The fact still remains the cell to cell transfer ia a faster route to progression.  I have to ask myself why some people are more prone to this transfer while others are not.  I may be misunderstanding the research.  The research suggests that antibody-based treatments aimed at interrupting the virus' progression may not work as well  because it won't work on the cell to cell transference.  Again thanks. A lot to ponder.

                                                                                                                                     Ron

                                  
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Avatar_dr_m_tn
The reason why some, particularly young and very healthy - like a historical example the whole eastern Germany womes olympic swim team- persons clear the virus is,

( that is at least the the current belief according to analyses of their immune responses and repertoires) ,

that they have a rapid and effective  class I and class II T cell response combined with an effective innate response (to which the virus has not had the time to adapt)

.that it able to overcome the viral dynamics of replication in its speed and vigor, BY KILLING INFECTED CELLS OR ELIMINATING THE VIRUS INTRACELLULARLY.
There is some contribution of the antibody response, but it is, as outlined, of minor importance.

There are - with the exception of the HCIG and monoclonals  that I, in the above post, mentioned - no antibody based treatments. IFN/ riba is not an antibody based treatment modality, but uses the other described pathways, together with HCV hypermutation and possibly generation of new traceable epitopes,
Direct hepatocyte to hepatocyte HCV transfer might well be an alternate mechanism to spread the virus. If that would be all the virus had, imagine how slow it would be to spread through the liver instead of showering the liver with its offspring, coming from all sides from the blood.It would be so slow, that the aforementioned immune mechanism would be mostly able to selectively kill the infected cells in time. Remember it is a race between reinfection and elimination of infected cells. it is the difference between a fire spreading from house to house or being spread all over the city by trucks using the streets throwing out burning ambers or by tornado like winds.

And also, please do not forget the importance of rapid threedimensional spread  in the blood of adaptively mutated HCV to far away places in the liver , giving its evolutionary power the practical mechanism to perform.
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Avatar_f_tn
Long-term follow-up of patients who have cleared hepatitis C virus (HCV), either spontaneously or after successful therapy with interferon and ribavirin, suggests that the likelihood of recurrence is low. This conclusion is based on analysis of HCV RNA assays. However, HCV RNA assays have a variable range of detection, especially at low viral levels, and no assay results can completely eliminate the possibility of the virus's presence. Some evidence suggests that HCV is not only present in blood and liver, but also may be present in cells of the lymphatic and central nervous systems. If these locations harbor virus that is undetectable by standard assays, that could have important implications for disease recurrence. HCV antibodies can persist up to 20 years after resolution of clinical infection, suggesting that the virus and its antigens may persist, but at extremely low levels.


what about hcv in the brain and spinal fluid? like HIV this is a virus and it replicates and is latent in ways healthcare does not to date understand.  To state any person with "chronic" HCV can EVER completelyt clear this VIRUS is a falicy.  WE are not there yet, not by a long shot.

you post some correct and interesting information, but your not being as realistic as the facts and "research" shows.
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Avatar_dr_m_tn
While the "virus' or some special variant or remnant of it, might not be completely cleared from the body, it is under permanent immunological control as several other "chronic lifelong viral infections", eg  EBV, CMV, acutely "cleared HBV".  The so called SVR - HCV undetectable by high sensitivity assays - is now considered stable in over 98% of the ones who have "SVRd".

The clinical/health importance of the "HCV remnants"  remains to be explored and understood.
I was maybe one of the first to bring the fact of some HCV persistence to the attention of this board, about a year ago.

Could you please indicate the sentences in my above post that are not "realistic"?
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so you are saying that these 98% with SVR undetectable are "cured"  In this 98% of the "cured" how many years was the HCV virus latent?  what would you consider a good average latent time period? 15, 20, 26, 30 years before the initial diagnosis.  So in your thesis have you considered these 98% of the "cured" in 15,20, 26, 30 years down the road?  Have you considered where else this virus may or may not have traveled within the human body that might affect homeostasis and produce a negative result.

I have just explained in a "realistic" way why some of these technical and microbiological posts you place on this blog are NOT realistic.  The data is not in.  If the "virus" (key point) can remain latent for so many years how can you jump on the band wagon and use these percentages why don't we wait say at least a minimum of 10 years and check back with these 98%.  then you might have your first real number that you can begin to put a % next too.  I am not a pragmatic person, but I did take microbiology in large content in college and I understand the full context of "virus"

also remember the difference in replication between Hcv and Hbv,

Lanier
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Just as an add-on, and not to be argumentative at all, but I have been trying to bring attention on the forum to the "post-SVR potential" for some sort of ongoing virus, or even 'dormant' virus, for over four years now.  My persistence (pardon the pun) has caused some controversy, and has provoked much discussion on both sides of the issue, here on the forum.  Although I do not come at it from a strictly bio-scientific approach, since that is not my background, I do make a range of observations and conclusions based on both inductive and deductive analyses.  I am quite convinced that there is some additional form of ongoing infection, and possibly other sites in the body where the virus probably continues to lurk at extremely low, and currently undetectable levels.  I won't go into all the details of my observations, and analyses, nor the supporting research that I have reviewed, since we have already aired all this information over the past few years on the forum.

Of course I cannot prove my conclusions, since I do not have the clinical resources available to pursue validation...but expect that ongoing research into the behavior of the virus will ultimately clarify and support in some way many of my concerns.  I think that there are also some obvious 'clues' to HCV's wider footprint, when you look at the current literature regarding lymphotropism, sialotropism, possible gastric fluid infection, joint and connective tissue infection, and most likely brain and CNS infection.  Additionally the list of extrahepatic symptoms, and affected organs/systems, all point to something beyond the effects of liver damage, and beyond cytokine overproduction and attack taking place in many of those with active HCV.  The fact that many who 'eradicate' the virus continue to experience many of these extra-hepatic symptoms on a long term basis, and also fail to clear many of the HCV antibodies over long periods of time, all point to a suspiscious viral behavior.  

I will also add that studies on the 'spontaneous clearance' group also point out a pattern of long term physical problems, including fatigue, memory problems, depression, joint pains, etc. over many years, and even decades, long after viral clearance.  Most of these individuals cleared the virus during the 'acute' phase, and were not long term or chronic sufferers.  What are we to make of the resulting long term physical problems that seem to be inherent in this group?  All due to a one time cytokine and immune system burst to rid the body of the virus???  I am very dubious about that sort of reasoning.  That would imply that every time our bodies fight off a severe viral attack (flu, viral pneumonia, etc.) that we will have lifelong physical problems and after effects as a result.  I am not aware that this frequently happens after a severe viral infection.

I only want to make the point that there may be much more to understand and identify regarding this virus, and there is a ton of behavioral, anecdotal, and recently also research evidence prodding us to take a more open minded look at this insidious virus.  I very much appreciate all the wonderful scientific information and commentary that you contribute to this forum, and I look forward to hearing much more from you as your research progresses onward.  Your analyses bring to us a very precise, and scientific approach for forming our knowledge base.  Thank for all your diligent time and efforts.  I hope that you do not mind the fact that many of us don't shy away from debate though, and do so with our own, sometimes "world acclaimed" doctors and viral experts.  I think we all have something to add.

DoubleDose
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I was wondering what your opinion was on something I was thinking about. There's a recent thread where dointime was "bummed" about being stuck with a telaprevir resistant virus. She was in the prove 2 group that received IFN+VX950 without ribavirin. She of course experienced a viral breathrough without the riba, and then was later taken off the VX950 and continued on with IFN and riba. She went UND again (after a month on ribavirin I believe(?)), but eventually experienced another breakthrough. She then discontinued all treatment. As you obviously know, one of ribavirin's primary modes of efficacy is thought to be its ability to hypermutate the hepatitis C virus. Overdriving and destabilizing its normal mutative processes which ordinarily serve its adaptive survival interests (especially in regards to developing drug resistance). Considering this (probable) hypermutative function of ribavirin, do you think exposing a telaprevir resistant virus to both ribavirin and IFN for a few months (without telaprevir in play anymore) would have any effect on the virus' retention of telaprevir resistance? In other words do you think it might be possible for the clarity of the genetic feature that gives the virus its telaprevir resistance to be disturbed or disrupted in any meaningful way? Do you think the post telaprevir ribavirin+IFN dosing period (which lasted a few months) that dointime (and others) underwent may have helped shift her virus away from telaprevir resistance in any way?

Thanks in advance for your thoughts...
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Oh god here comes the viral persistence (oc)cult nuts. GIVE IT A BREAK GUYS! And DD I've never seen any fully repeated and widely acknowledged evidence that acute "clearers" have all these mysterious and murky symptoms you're talking about, and I've known a few who've cleared spontaneously too. Furthermore, HR never outright dismissed the persistent low level stuff Castillo came out with (that you guys cling to with such fervor). In fact I recall him saying the study was conducted at a very reputable Spanish clinic and the results were impossible to refute based on what he knew at that time about it (much to my dismay). If memory serves he said the jury is still out, but the Castillo findings were not to be dismissed without more study...and that was like a year ago! And DD I believe you were in on that conversation as well, don't you remember? So why do you guys seem to gang up on HR when he says anything even *remotely* suggestive that may not fully support your viral persistence religion? DON'T RUN HR OFF YOU JERKS! And for chrissakes give your "oiiiii, I've got a paaiiinn!!" stuff a break!
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That's an interesting idea mre.

I am wondering about the state of my 'viral swarm' too but from another point of view.  You said in a previous post that telaprevir might still be used in the future to rapidly cut down the reverted wild type virus, even if it has no effect on the resistant strains.  I got the impression from HR's post that ALL of the viral swarm 'remembers' the drug, including the reverted wild type, and the instant it meets it again it says - hey guys, it's this sh** again, everybody mutate pronto.

So how does it work HR please?  Would telaprevir have some effect or no effect whatsoever if it were used a 2nd time, say after 5 years?  I just remember how it was after the breakthrough when I was eating the stuff 3xdaily for another 8 weeks and it did not even dent my viral load.

dointime
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And here's to you as well, pal.  Sounds sort of like you just lapsed into a 'pseudo-borderline' tx rage spasm.  Hey, don't over react to some casual opinions...I'm sure HR won't be offended by my comments.  Anyway, just to respond to only one of your less than knowledgable rants, here is the deal:  Several studies of 'spontaneous clearers' looking at large numbers of people over decades of post-clearance time span found that something like 90%+ still experienced unusual symptoms, as mentioned above, in line with typical HCV symptoms.  Sorry it didn't hit you well tonight...maybe go
take a hot soak, or pop an AD, but please calm yourself down.  You are sounding like someone who used to post on the forum, that could not tolerate opinions out of line with their own beliefs.  And if the scientific professionals and researchers who are documenting persistent virus in SVR's, of which there are more than a dozen different researchers by now (look for links in the past from TnHepGuy, Willing, ME, of course, and others), if they are "nuts", then you are just telling us something about yourself.  Relax, the world is not coming to an end.

DoubleDose
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151263_tn?1243377877
The remarks I made were mostly made towards lanier, who was being rude and aggressive towards HR (and with a poorly thought out line of thought at that). You're a much nicer and more reasonable person, and always have been. So yeah, maybe I shouldn't have lumped you in with him. And I really don't have the slightest interest in going over the uber over hashed viral persistence theory that has essentially become a religion with certain people here (which obviously includes you).

But here's a newsflash: THE JURY IS STILL OUT. It has NOT been conclusively and irrevocably determined by a wide panel of scientific experts using repeatable tests in a variety of places that absolutely proves once and for all low level, ongoing viable viral persistence and reproduction occurs after SVR-ing (naturally or otherwise). Yes there have been reputable researchers and research that have strongly suggested that this may be happening (namely CASTILLO et al). But his results have not been widely repeated by enough scientists (apart from him and his lab) to convince the hepatology world in general that this "viral persistence" is what it appears to be according to Castillo. Maybe it will turn out to be a fully vetted theory in the future? I'm not saying it won't, absolutely possible. But for now there's an awful lot of unanswered (and very obvious) questions that neither you nor anyone else has good answers for that flies in the face of this theory. Only vague, poorly supported, amateurish and almost conspiracy like assertions are used to support this case (which you honestly seem to *need* to be true). Good science doesn't depend on someone needing something to be true. And you have made many comments since I've been here (for over a year now) that frankly speak of a possible neurosis concerning how contagious you seem to think HCV, or its symptoms are (which connects with the aforementioned "need" for truth). I don't believe it's normally possible to make people sick with HCV-like symptoms simply by an HCV infected person having casual contact with uninfected people, even on an ongoing basis. Sorry, I just don't believe that! And guess what, I'm sure nearly all qualified hepatologists don't either. Not only that, most people I know who actually HAVE an active full blown chronic HCV infection don't have any symptoms anyway. I'm one of the few I know of who actually DID have symptoms from my HCV. I've since treated, suffered during treatment, stopped treatment and now have cleared the virus. And guess what? I feel great, I feel CURED. I feel fantastic and haven't felt this good since I became infected way back in 1983. Why do I feel good now that I no longer have the virus, but felt like **** when I did have the virus??? Oh mystery of mysteries!

I'm truly sorry that you have the symptoms that you describe after achieving your SVR. I can absolutely believe that you may have some form of post tx automimmunity issues that may explain your symptoms (as occurs with many people after tx). Or perhaps your longstanding HCV infection has somehow altered your immune system in a way that has caused you to experience these symptoms, I can believe that's possible too. But the whole concept about the casual contact ->low level immune response -> HCV symptomology?? That's a real reach man, and you reach for it all the time, and you tie it into the viral persistence stuff. It's your bogeyman is what it is. You need to remember that although it's possible the viral persistence theory may turn out to be correct in some way, it's also possible it could be outright disproved or recharacterized into something none of us can predict or expect. And that much of what you constantly speculate about concerning the casual contact transferrence of HCV-like symptoms is a pipe dream that you're using to try to explain something that you're convinced exists when that something may either may not exist at all, or may have origins in something else completely unrelated to HCV (including psychological factors).

DD you're a good guy, a thoughtful and intelligent contributor here, and I was too harsh in what I initially said to you. But the whole persistence thing and the casual transference thing is overdone. I normally don't care if it's discussed, and you certainly have a right to discuss it and I even enjoy chatting about it sometimes too. I just don't like seeing HR grilled over it by testy amateurs that basically don't know what they're talking about (and I'm included amongst the testy amateurs, incidentally). Especially when he openly acknowledged the tempered legitimacy of the Castillo findings a damned year ago anyway. Most of us here don't want him fatigued by the aforementioned testy amateurs wearing him down with irritating and stupid posts rudely challenging his thoughts on important issues (that the rest of us would like to learn about!). He's a very special and rare person, and we'd like to hear what he has to say without him having to constantly defend himself over silly or trivial matters. And yes I'd put the whole issue of viral persistence, as it's being brought up here so far by lanier and to a much lesser extent you as being something that HR shouldn't have to "defend" against. Lets remember he's the extremely accomplished hepatologist, and *we* are not.
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Avatar_dr_m_tn
dointime:
I got the impression from HR's post that ALL of the viral swarm 'remembers' the drug, including the reverted wild type, and the instant it meets it again it says - hey guys, it's this sh** again, everybody mutate pronto.

No, often with this mutations only a small portion often remembers the drug, this depends very much on the mutations effect on viral fitness and the degree of secondary, additional compensatory mutations developed by the primary mutant to regain fitness.
The "archived resistance" concept .states that at least a small, even quite small amount of the resistance mutaion will always standby, to become important again when the specific pressure rises again.

With the Tela mutations they have found various pattern yet, the analysis of reduced fitness mutants  - vs  percent returning to wild type is an ongoing endeavor for years to come.
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Avatar_dr_m_tn
lanier:

so you are saying that these 98% with SVR undetectable are "cured"?

No I was NOTsaying that.

Read again,  it says
The so called SVR - HCV undetectable by high sensitivity assays - is now considered stable in over 98% of the ones who have "SVRd

The technically defined HCV UND state is what is, experimentally proven,durable. That is the definition of SVR.

I hinted that the virus is likely still around::
might not be completely cleared from the body, but it is under permanent immunological control as several other "chronic lifelong viral infections", eg  EBV, CMV, acutely "cleared HBV".
I wrote in length in this regard a year ago, with DD heavily in the discussion group..I have a lot to say about that hidden remnant. But not all in one day, on one page.

We do know ,lanier and DD,  that these viruses " under immunological control" are still - logically, a constant source of some minor immune activity - with some bodywide immune activation - often leading what is called "chronic fatique syndrome etc".

Would you please remember that the original reponse in the beginning was to the BBC article, to explain its limitations?? That not all finer ramifications of the HCV virology/immunology story can be addressed in detail every post, when the BBC issue was mainly addressed?

Lanier what is your detailed response to the BBC article?

And what did you mean in the given context by your statement:
also remember the difference in replication between Hcv and Hbv.

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Avatar_n_tn
some time ago i was examining the icosahedron shape of the hcv capsid.my question is this.
is this shape significant to conserve energy,  fool antibodies, but also as an archive for the mutations that are replicated.  do you have any insights on the significance of this beautiful shape?
thanks.
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On a lighter side...and I know this probably belongs on the *other* side, but I figured you probably don't read the other side...lol....but I was just wondering if you caught this program on PBS, on Nanoparticle Theraputics, the name of the program was "Curious"

http://blog.targethealth.com/?p=404

I figured you might know him or know of this guy, Mark Davis. Wonderful things they are working on, it made me a little teary-eyed. I used to look on these things dispassionately, and think these types of programs *interesting* from afar...it's another to actually be a patient. I see programs like this in a whole different way now. So happy that we have researchers out there helping us:)
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I do understand where you are coming from, and am pleased that you clarified your comments.  I also understand that my more 'off the wall' theories are not at all accepted (by anyone inside or outside the HCV community), and appear to be highly unlikely if not impossible.  I recognize this, and also understand that I may well be totally wrong in my concerns about casual transmission through an atypical form of infection.  So, believe me, I am not trying to claim that I have some special knowledge on this one, just that I have observed some curious things in close contacts, and intimate partners, and that something MIGHT be a common thread.  

One major hepatologist is also doing a large scale study regarding this issue, and is looking at the "cellular immune responses to HCV'  in family members and intimate partners, including past partners, I believe.  The concern underlying this study is that there has been shown in previous, small research studies, a very high % of close contacts having this positive HCV cellular immune response, as compared to control group individuals who have almost zero % positivity on these tests.  Now, wherher having a positive 'cellular immune response to HCV' means anything about having an active viral infection, or what the test results mean regarding health, symproms, future potential for an active HCV infection, etc. are all completely unknowns.  But the study in and of itself does support to an extent, my concerns about some sort of familial, or intimate partner 'fallout' from being exposed to HCV.  What this really represents is still anybodies guess.

I appreciate your clarifications, and as you know I rarely let my 'emotional' or assertive side show on the forum, I did kind of react in a less than friendly manner to your post.  If your comments were not aimed at me, fine, but still I think you also could tighten up the inflammatory lingo, and just respond to the issues in a rational manner as well.  I think we are all looking for the same things...better knowledge, treatments, a fuller understanding of why different problems occur, either pre-tx, during tx, and post-tx....and how to best address these issues.  

Let's all move forward rather than point fingers.  It does none of us any good to stir up animosity.

DD
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I also remember very well your many comments regarding the potential for immune system control over a potentially minute amount of remaining or dormant virus, as you mention in your post above.  That is why I did not feel that my comments were in any way contradictory to your observations or beliefs, and did not want to be perceived as disputing your earlier comment, but just clarifying what the overall understanding actually was regarding SVR and 'eradication' versus 'immune control'.

I think that you have provided so much intricate insight about the virus, that it would make sense for us not to take one or two comments that you might make, out of the context within which they exist.  That is, there is a much larger and more detailed discussion of viral behavior underlying any of your comments, and much of that information has been shared by you over the months on this forum.  I certainly don't want you to have to reiterate your previously stated positions or assumptions everytime you respond to an issue, or make a statement.  We should all make the effort to review all the prior posts through which you have provided a far fuller picture of the virus and its behavior.

Thanks again for your contributions.  

DD
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Avatar_m_tn
lanier,

I hope you don't take this as piling on, but I hold some different views mostly formed from the available studies,articles and data I've read over the years and thought I'd run a few ideas up the flagpole to see if anyone salutes.

"In this 98% of the "cured" how many years was the HCV virus latent?  what would you consider a good average latent time period? 15, 20, 26, 30 years before the initial diagnosis."

There is absolutely no evidence to suggest HCV has a pathologically-defined latency period. All evidence suggests it is active from the moment the inoculum enters the blood. The average  length of infection before diagnosis is 20 years if that is what you are referring to---this coincides with the same avg length of time that CHC becomes symptomatic in the majority of people.

There are many people who were cured over 10 years ago. And they are still cured. There are lookback studies online that support this. I know two personally who still are active in the local HCV support groups who cleared over 14 years ago.

As for SVR, I have never seen one documented case of relapse beyond 24 months. I challenge you or anyone to find a documented and verifiable case meeting this criteria. I've been making this challenge for 7 years and so far I've not been presented with one.

Thousands upon thousands have treated in this country alone. Worldwide, it is over a million easily. How come no records exist documenting a post-SVR relapse beyond two years ? Don't you think that is a bit unusual if it indeed were part of the natural history of HCV ?

Not all viruses are created equal. HBV is not even a distant cousin of HCV, and any comparison is apples to oranges.

As far as 'hiding' out in the body, that is highly unlikely from what I have studied. The same immune system that needs alot of help to clear the virus upon initial infection is not likely going to be able to suppress the virus once the therapy ceases, in my opinion. If this were true we should see and hear of hundreds upon hundreds of relapse cases that coincides with periods of weakened immune states post-SVR in these patients.  If the immune systems of those who have cleared should come under heavy attack from another virus, like a serious flu mutation for example,  you would expect to see a parallel pattern of relapses in those patients. After all of these years of study no evidence exists that shows that this occurs. With a replication rate of nearly a trillion copies a day it wouldn't take alot for a severely compromised immune system to fail against the onslaught of both wild type and QS production. Each virus is capable of producing millions of QS during its meager short existence (a half-life of 2.5-3 hours) overcoming the immune response in over 80% of CHC individuals. Furthermore, hiding out will not accomplish the main purpose of the virus. Replication and transmission.  As soon as the immune pressure is off (cessation of therapy) should any virus remain it would be back to business as usual in its quest to continue the existence of the genus . It cannot do this by going dormant. Transmission by blood only is a terribly inefficient means of infection. Opportunities can come few and far between for the virus  to infect a new body, and it would not be in the 'interest' of the virus to hide for any amount of time  with so many low percentage vectors for transmission available.  IVDU which is now the leading cause of HCV infection is still not an efficient means for infection as it is practiced by a very small minority of humans as a percentage of the overall population on earth. So HCV does not really have the luxury to hang out too long if it doesn't want to miss any opportunity to infect a new body in its quest to preserve the continuance of its genus. Furthermore the amount of inoculum has a direct bearing on the immune system's  ability to fend off an initial infection. If it wants to have a decent chance for transmission and continued existence in the new host body, it has higher chances to remain in existence as the initial amount of inoculum is increased . So, if it wants to continue its existence it will have to come out of hiding and get back into some hepatocytes where it can function much more effectively, which in turn would put detectable amounts of viral particles into the sera. This would be a relapse which brings us back full circle to my challenge.

regards,
Mr Liver
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your remarks about apples and oranges is exactly what I was saying to the hepguys comments.  
hcv has a single strand of RNA and is enveloped.  It is capable of rapid genetic variation to evade the immune system, this along with the relaity that it cannot be cultured in vitro complicate the finding of an effective vaccine.  I have no doubt there are a small percentage maybe 30% on the high end who have been able to sustain a favorable respone.  

what is all that "gaggle" about "inefficient transmission" I do not need to know how this virus is transpeffered.  it is a blood born virus and that makes it by definition difficult beyond cure to date.  Why are you wasting all the time explaining to me the response of this blood born virus after treatment stops? and "infecting new bodies" I am not writing a science fiction novel here, I understand and can process all the "correct" information.  

blood born pathogens travel how....let me see...in the blood maybe.  good grief.  do you have any blood in your brain?  
only a minority of the people who are carrying this virus even know they have it today, it is going to be another pandemic in our stresed health care system.  It is not a well understood virus and there has not been enough research into the virus to even infer we will have a reasonable long term treatment for years.  All the hog wash you read about the newest flavor is just that.  I want there to be a real solution, but I know that unitl it becomes more important than "viagra" to the pharmacutical companies we are all screwed without an erection.  I could not completely read your "story" since it was so off topic in many areas.  All I was saying was the 98% number is baloney and the hepguys using any correlation between HCV and HBV is ridiculous.

Pile on all you want, I just wish you would put in a more readable text, I have trouble with processing in general, my ability is affected by my disease.  It is one of the many frustrating parts of this virus, if you are educated in anatomy or microbiology then you are often self aware enough to "see" what your deficets are even though you cannot change them.  I wish everyone who has even one year of freedom after this TX they are pushing now all the best, but I believe until more people step up and start asking their healthcare agencies "why" more then there is not going to be the budget required to help the many of us who do not "clear" with current remedies.

I do not think this virus "hides out" anywhere, I think it affects many chemical responses and synopses within the brain, I think it affects the liver, the kidnys, the pancreas, the gall bladder, the bile and bile ducts, and the current treatments offered often exasserbate joint pain, integumentary issues and chemicals and nerons synopses within the brain.  This virus never needs to hide.

lanier

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I happen to like that someone of your intelligence is posting on this forum, because we share some views re integrative medicine, etc and a person like you can give some credibility, hopefully, about alternative views in this area... I hesitate to say that any one poster deserves more "respect" then any other poster, etc...I like to be egalitarian in my views with respect to these matters, ideally anyway....

But I suffer from this disease just like everybody else here, cept those who have SVRed...and I happen to know HR offline, because I was lucky enough to be able to obtain a fibroscan from him, and we live in the same area, etc...I like to think that we have become friends as well.

There are other members here who were able to get a fibroscan from him as well, but maybe they don't want to enter in such a contentious discussion, I can certainly understand that. Getting into contentious debates here can lose it's charm after awhile, and we're not all up to it - all the time (thank God.)

I'm pretty mouthy myself in case anyone hasn't noticed, lol. And at times I speak out of line, cross a boundary, if you will, and for that I'm sorry....because I think it benefits us all to be as polite as possible, even if we fervently disagree on any given issue. Makes the whole board a more pleasant and informative experience for everyone. I realize some people find it harder to reign in their emotions, for a variety of reasons.

But all in all, I'm not the only one here who knows this man personally. If my own credibility is in question, I fully understand that, because this is an essentially anonymous board with most of us using made up monikers. Though I have been coming here for over a few years now, and I know plenty of members offline, if that means anything.

But please afford this man some respect. He co-owned a company that provides us all with some much needed testing devices, and a variety of other things that help many hepatitis patients. He has patents all over his walls of things he has INVENTED. He an MD, but he found it necessary to get out of clinical practice, and help people in much more wide-ranging ways. He continues researching and analyzing, hoping to make our patient experiences and outcomes....better.

I would just like to point out that this man comes here mostly out of pure altruism, and a need to find out the *patient experience* of this disease..... I wish all the medical professionals would care as much "what we think."

He, by no means, is coming here out of any kind of monetary consideration as someone might of thought (I realize not you.) Though of course, that's a legitimate question. He sure doesn't need the money, he's perfectly well off. BELIEVE ME.

He's a realist, and he realizes that some people here might look at his motives with suspicion, after all, many of us are not used to medical professionals coming here among us, only wanting to help and find out our stories. I don't think he has a big problem with that. But he's not a man to toot his own "proverbial" horn so to speak, so I'm coming on here to clarify some matters, sorry if I offend him or anybody else. The only thing I've heard ever heard him complain about, is us not doing our homework and putting him into the search engine here, to find out if he's answered a certain question more then once, his time is indeed valuable.

It's been my experience that people who toot their own horns the loudest, are people who are usually insecure about their own accomplishments or place in the world, which results in a need to do this. HR does not need to do this. The guy's got nothing to prove and he remains a gentleman under most circumstances here, from what I've seen. His vast knowledge does his talking for him, one would hope. So, of course, he doesn't get offended if someone doesn't agree with his opinions, he probably expects that. We are all ultimately free to believe any opinion we might choose to believe, after all.

But what I'm saying is, please show this man some respect, if you knew who he is and what he knows...and what he has done and what he proposes to do for us, I assure you, you would naturally want to show him some respect yourself. Respectfully to you. Let me climb down off my soap box now lol, and enjoy my weekend, I wish the same to all of you.
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who are you praising here dear girl.  I praise him too, if you want.  If he is an MD or a dishwasher makes not a tinkers damn to me.  My education does not help my virus run any different course than anyones.  I will never not respond to generic remarks that in my own experience and education I understand to be bunk.  sorry for that in advance, and if this "person you are speaking of is helping people God bless him, I think we all try to help each other with our own experiences we bring to the table.  and having worked with MD's all my adult life I see them for who they are eyes wide open.  Thank you for saying whoever this is is a good person and understand I never mean to imply anyone here is not a "good person"  I just think many are blindly following a less proactive path in their own well being than maybe they would if they saw things from the inside out.

I hope you have a great weekend and cudos to whoever it is you want me to "respect"
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I'm not asking you to agree with him because of who he is, like I said, he's not an unreasonable man, he fully expects people to disagree with him from time to time (but knowing him, boy, do I know that you better know enough to back it up, but that's just my personal opinion).

I'm just asking that the members here just respect him, that's all. He doesn't HAVE to come here, and it's not like we have a lot of REAL professional experts here, no disrespect to anyone....One of the reasons he likes it here is because there are a lot of bright patients here anyway.
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I have no clue who this person is you are speaking of and I think there may be more REAL professional people here than we could imagine, what constitutes a REAL professional?  how many years in college, work, life experience?  I respect any person on this blog for having the guts to talk about their experience, I do not blindly respect anyone here for any other reason.  If he "helped" you good you.  I am not a "patient" I am a person a proactive "client" who has the right to question and develop a rapour with anyone else here who puts forth an opinion.  I mean no ONE any harm.  I repeat I am NOT  anybody's "patient" that is "old school" I am self aware and just happen to also have a medical health care background.  I will never be anyone's patient, I will accept their advice and discuss MY options and use both to live with the best quality of life I can muster.  Please dear lady I am 50 years old all grown up and "who he is" his stature or place are all the more reason to develpo educated questions from my perspective.  and I wish him goodness and happiness and whatever else it is he needs if that makes you feel better.  If he is a medical doctor and over 40 then he has surely noticed more "clients' ( what we call them now days) who question and ask, his ego must be strong enough to endevour to answer these questions and I am sure he could care less what I write or say.  

regards
Lanier
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please don't tell me it is the blogger who was "explaining" viral transfer, oh how I hope that is not the person you are going on so about.
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youre not listening to me. My own doctors respect him. He's got more degrees to shake a stick at. In other fields of knowledge besides medicine. If we were basing this stuff, on just credentials alone, fogetabout it.

But I'm not saying to agree or disagree with anything he says based on these facts. Disagree with him if you have a mind to, that's your right...but you were taking a very demeaning tone with him, beyond your disagreement of any particular issue, *and that is what I was objecting to* Nosy Parker that I am.

Otherwise, rock on. He'll either debate you, or not. Doubt if he has time to split hairs, or get into  circular arguments that go no where, much like the one I'm having with you, lol....

no disrespect...I'm simply pointing out the man deserves respect. If you choose not to believe any of this, bully for you. I'm done. He's probably really annoyed at me anyway, for carrying this on to this extent anyway, my bad.

Sometimes I'm like a mama lion, protecting her cubs, when it  comes to my friends. I'm a Leo after all. Speaking of which, to change this whole line of discussion, please??? what do you think of Astrology? just kidding, peace out....have a good weekend....
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well it must be you that in the fountain of knowledge I have managed to upset a few people about.  So with my kindest and most respectful regards to you if you are living the dream and a HCV client I say I am sorry for anything I may have responded to your "blog" that offended some others.  I admit I am not here from years ago.  I only found out in recent years I had this gift and I am in healthcare, have worked in hospitals emergency rooms many years of my life prior to 2005.  I am afflicted now not only from trying to treat, but my virus itself.  I guess you have been "here" for years "helping others.  I never wrote on a blog, chatted to stranger online in my life until this place somehow crossed my path when I was researching my virus.  I understand that "tone" is hard to see.  Please whoever you are a PHD or a dishwasher who has a gift, accept my perspectives from a passive perspective, I am sick, and I write without "tone" in many cases.  

Lanier
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"I have trouble with processing in general,"

If you do not know the term 'inefficient means of transmission" then you have not studied virology.

HCV has been cultured in vitro for 2 years now. Where have you been ?

Your premise about pharmaceutical companies is what is hogwash. You don't think there is incentive when the worldwide infected population is nearly 200 million ? There have never been so many HCV drugs in the pipeline than there is now. Why are so many drug makers competing to become the first with a more efficacious treatment if its not important to pharmaceutical companies ? Here's another challenge you will not be able to fulfill----name one disease that has more drugs in the pipeline than HCV currently does. Now why is this ?  There is no other explanation for this other than the potential for a big payday if a company is the first to market with a better tx modality.

" Why are you wasting all the time explaining to me the response of this blood born virus after treatment stops? and "infecting new bodies" I am not writing a science fiction novel here, I understand and can process all the "correct" information. "  

If you only had humility you'd be perfect. I agree It was a waste of my time  trying to explain to you just how wrong you are about completely ridding the body of the virus, and relapses occurring beyond 2 years post-SVR. Like I stated above find me just ONE documented, and verified relapse beyond 2 years.  The chance of being detectable for the virus again after one year of UND is 98%. This statistic is well documented and supported by tons of data. If you have contrary data or findings to support your contention that this number is incorrect why don't you share this info ? I also pointed out that studies DO exist concerning people who have been undetectable for OVER 10 years. As for crossing the blood brain barrier so does interferon.

If you do not understand that a virus is designed to ensure the survival of the genus then you won't probably don't grasp the concept that remaining in PBMC, or spinal fluid, or the brain, is completely antithetical to this goal.

Your reply was filled with personal insults, a sure sign that someone cannot support their speculative assertions. Relapses post-SVR and the claims you made concerning latency are merely musings on your part which are not grounded in scientific fact.

"I do not think this virus "hides out" anywhere"

"and it replicates and is latent in ways healthcare does not to date understand"

The purpose of a virus going into a pathologically defined latent state is to avoid detection while remaining in the body. So which is it ? It either does or does not try to evade (re:HIDE) by remaining in a latent state until the opportunity presents itself for it to become active. If the virus never needs to hide as you claim, then what is the purpose of viral latency which you contend is a feature of HCV ?

" it is going to be another pandemic in our stresed health care system."

The rate of newly acquired HCV infections has dropped 85% since 1991. Current rate of new infections in the U.S. is about 30,000 yearly compared to a high 16 years ago of 180,000 new infections yearly. Starting around 2016 the number of infected individuals in the US and Europe will start to decline rapidly as the last of the baby boomers cycle through. These facts do not support the notion of a pandemic. It matters not if half the people with HCV in the US do not know they have it. The infection rate is still 1.8% of the population
and as described above that number will be declining rapidly in just a few years. Your Chicken Little impersonation has no legs.

Lani you really do need to study more if you want to gain a more accurate and intimate knowledge of HCV. I can certainly understand how my post must have seemed like science fiction to you.
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Civilized and straightforward contribution. The issue of the existence and potential clinical importance of the "viral remnants"  of HCV found by many in high sensitivity assays - particularly in the PBMCs, is however quite complicated if you drive it to the detailed level.  Another time we might have the time to discuss its finest points. There could be lab artifacts involved - see prior discussion of PCR sensitivity and contamination issues. Reactivation under chemotherapy is indeed much more rare with HCV than that of HBV, but even  in the transplant setting, IFN/riba is often able to " clear" (SVR)  HCV, which is somewhat of a surprise, considering the immunosupressive drugs. But all this for another time.

I actually wanted to see how you responded to the BBC article, none has actually addressed that in any detail - this threads actual topic.
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Your continued support is noted and definitely appreciated. I do not always have the time to respond to disagreeing posts ( with my viewpoint that is) , which actually do not really disagree with what i said, in this case relating to the faulty "conclusions" of the BBC article.

Believe it or not I actually like to be found wrong in factual statements or conceptual ideas, since I am only interested in seeing the reality behind a natural phenomenon like the biology of HCV. In this case I was unable to detect any constructive criticism, however, beyond the reminder that HCV and HBV are different viruses. I was also reminded of the chemical nature of ribavirin and of the fact that not wanting to give out any brand names does no save you from the suspicion of being an owner of the company that you do not want to disclose. Three things learned in two days - that is not nothing.
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well i also hope you learned this.
that your comments are not only educational and a ray of intellect here but also that you are highly regarded and appreciated by all even if you choose to believe the 3 things you listed above.
i work with many bright MD's for over 30 years and have alot of respect for their fine education but not always respect for their lofty ego's that sometimes accompany it. i also can witness to many mistakes made by them. i do not judge, we are all human. i support our medical practice in this country with years of dedication just like you! an i will continue to do so until i retire.
i hope you remember the hope and appreciation that many have here for you even though most of us would not be able to argue on your level of education with your conclusions. gee, if that is the reason for coming here you might be better challenged with others who are an equal footing with you. i am not for certain and do not pretend to in any way. but i do exercise my right to question you. i have no suspicion of you as you have stated and i repeat my question was to understand if you had a bias to a mentioned product. you answered and i accepted. however you are not being fair to continue to use it as any reason not to enjoy the fine people of this forum.
please HR release your suspicion! no one here wants to argue with you! only to understand this disease and treatment the best to their ability. the fight against hcv is an enormous one for the people who suffer it. again i thank you for your sincerity to help us understand what it is we fight.
peace.
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I admit I do not understand a great deal of your posts...but I certainly do get your wit!  Bravo!
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There is no doubt this is one of the reasons this forum is such an exceptional place. It's because someone of your stature takes our questions and answers them to the best of your ability...our own Dr's, half the time, won't or can't do that. Thank you so much for sharing your research and your knowledge.

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"The "archived resistance" concept .states that at least a small, even quite small amount of the resistance mutaion will always standby, to become important again when the specific pressure rises again."

Again, most useful to get your answer.  Much appreciated,
dointime.
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Whrose:
some time ago i was examining the icosahedron shape of the hcv capsid.my question is this.
is this shape significant to conserve energy,  fool antibodies, but also as an archive for the mutations that are replicated.  do you have any insights on the significance of this beautiful shape.

Many viruses have capsid shapes similar to this. Its geometrical symmetry results from the need of the capsid proteins to self assemble into a continuous shell for the genomic material, with anchor points and functional structures on the inside and for the envelope outside.

The building block of the capsid - the core protein, has to not only serve as an anatomical vehicle but is in addition amazingly multifunctional, essential for viral maturation, replication and pathogenesis,

In addition to its  functions in the formation of the HCv virion it has several regulatory functions, including modulation of signaling pathways in favor of the virus, influence on celllular and viral gene expression , the tranformation and death of hepatocytes and its lipid metabolism.

It is certainly a miracle of molecular engineering, as nature has afforded to build it by quadrillion cycles of trial and error, it performs all these functions with one type of protein and it is also a key factor in causing oxidative stress to the hepatocyte, that hastens its death and apoptoses, leading to cytolysis and then Kupfer cells will respond to the cellular debris with activation pathways, that in turn activate hepatic inflammation, oxidative stress to the hepatocyte DNA, mutations in the cells genome leading ultimately to carcinoma of the liver.

This proinflammatory pathway is further a key factor in the so often mentioned activation of stellate transformation, that leads to the formation of the myofibroblasts that generate the fibers that lead to the progression of fibrosis. A few days ago an editorial in the New England Journal of Medicine by Jack Wands detailed the mechanisms, by which HCV leads to hepatocellular carcinome and pointed at the tremendous importance of the Kupfer cell activation by the aforementoined cell death debris recognition. If you read his editorial carefully you will see that blocking the proinflammatory pathway at the Kuper cell could make a huge differnce to the outcome of the disease, as was the case in the animal model presented in which Estradiol was able to block the Kupfer cell  activation to a substantial degree, leading to a difference of cancer in 100% of males vs only 30% in female animals.

Tell me what you can conclude from the foregoing  in regarding the importance to prevent leaky gut syndrome/ LPS production and release by proper eubiosis in the intestines?
In what way could, for instance,  the administration of N acetylcysteine (NFI) impact upon this pathway?
How could certain flavonoids and related compounds impact upon this part of the activation pathway and hence upon the risk for cancer and fibrosis progression?


The fooling of antibodies is as I outlined hiigh above at he beginning of this thread so as to reveal the silliness of the BBC article. . I recommend to work through it line by line. The key is the binding of plasma lipids to the hydrophobic amino acid tails of the envelope proteins, generating an outer lipid cout on the circulating virion that shields it from epitope recognition by antibodies.

The archived reservoir for the mutations is everywhere, but mostly in the viral RNA inside the cell, less in the mature virions circulating. It is like a thousand unrecognizable future terrorists being inside their safehouses or on the road or flying around - where is the archive, the reservoir - its interspersed, everywhere the viral RNA is.



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Keep coming back.
(pretty please)
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Mr Liver
As for SVR, I have never seen one documented case of relapse beyond 24 months. I challenge you or anyone to find a documented and verifiable case meeting this criteria. I've been making this challenge for 7 years and so far I've not been presented with one.
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This one is borderline but shows that Relapse after 2 years is possible if extremely rare.
Its right on the 24 months but I am sure I have come across the same only it was 7or 8 years after SVR.
http://www.ispub.com/ostia/index.php?xmlFilePath=journals/ijge/vol5n2/hiv.xml

Abstract
It is known that sustained virological response in patients with chronic hepatitis C is associated with sustained elimination of hepatitis C virus and that late relapse after SVR in HCV patients is doubtful. Α 47- year old man with chronic hepatitis C genotype 3, achieved sustained virological response after combination treatment with pegylated interferon and ribavirine for six months. Sixteen months later non Hodgkin's lymphoma was diagnosed. After successful completion of chemotherapy for non Hodgkin's lymphoma he presented with HCV infection recurrence of the same genotype. Retreatment with the same schedule resulted in normalization of aminotransferases and disappearance of HCVRNA from the serum. This case suggests that recurrence of ΗCV infection in a sustained responder may be probable after immunosuppressive therapy. Prevention is currently impossible but retreatment may be successful.

Swain et al reported that in only seven out of 845 patients who had been successfully treated with interferon monotherapy or combination therapy HCVRNA was detected after 391- 1076 days off treatment ( 20 ). None of these were in patients taking combination therapy for 48 weeks. These data indicate that the late relapse after SVR in HCV patients is very rare. In our patient recurrence of HCV infection happened after chemotherapy for non Hodgkin lymphoma,
24 months after the end of successful treatment.

CS
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I do not know what in the heck you are trying to teach me?  I took enough college classes to understand I have a lowly bachelors in nursing with a pecialty certificate in geriatrics and Alz.  I use the word "process" to articulate, my cognition slowing down, my own failure understand as quickly as I used too.

In vitro we have to denate that and please cite your information.  The last very interesting micro class I took was at Nova University in Browad county and I have my text the class was in 2003, the text is a 7th edition torte - funke- case that is where my "information" came from.  I was not diagnosed at the time and therefore if this information is incorrect and you show me where to read otherwise I would say "thank you"

I am do not nor will ever be convinced speaking just from personal experience that this virus does not "travel" within the body and although it may not expressitself in the exact same way when it appears again it is my firm and EDUCATED belief that it is often times expressed through other diseases.
I live this virus, I know it is affecting my integumentary system, I know it affecting my immune system, I know it is affecting my cognition and the list goes on.  I am not alone I do not believe it is only me who  has developed these maladies as a normal part of aging.  ten years ago I was a person who dived, and repelled and lived a very active life.  Since 2005 when the disease surfaced and since treating I have developed many health issues.  Prior to diagnosis I had many health issues through the years. shingles, colitis, anemia, still have a very low platelet count to date after treating I developed integumentary and cognition issues I never had prior.  My symptoms and blood counts went crazy in areas I will not go into at this point.  I was acute by 17 years of age.  I have had my biopsy and ct scans and blood work and typing and viral loads done.

when I say "latent"  all I am saying is the virus is mobile to other systems.  when I say "does not need to hide" it is an expression, I have trouble with "tone" here I admit that.

I believe that like HIV this virus does tranfer itself to the cerebral spinal fluid and I believe it does cause other disease.  I can not say I have read all the studies and every current clinical outcome, I can say I am a health care graduate who loved the field and is self aware and knows from the inside out this virus is not going anywhere soon.

We have a whole new generation of the rich and famous to look forward too being carriers and they are no different than you and I, we were living the life like super hereos who could never get "caught" I never knew there was HCV when I apparently got it.  HIV mutates, do you think the young people who are getting the virus today by snorting or shooting in 30 years will be carrying the same HCV we are?
Your 1991 85% drop is BUNK, snorting in the new way our little darling are being infected and I just read your entire post and your a moron.  your telling me that you can not in all your "internet" education research find another clinical pharmicutical company that has more studies going in research for HCV.  Lets see I worked in healthcare for the better part of 20 years, alothough I have not read any internet hogwash, I rely on TEXT BOOKS I say just for fun look up a company called MERK, tell me what they are spending their clinical rsearch on?  and your "current rate" date where do you think it COMES FROM....LETS SEE BLOOD WORK, and lets just say for the fun of it.  that oh the average 20-30 year old who has snorted some good stuff in college or because he/she could afford it, has a normal liver enzyme....So he/she goes in and says 'YOU BETTER TEST ME I SNORTED SOME ILLEGAL DRUGS" AND I MIGHT BE INFECTED.  your living in a dream world those numbers you "quote are the same **** different day.  I had NORMAL liver enzymes 99% of my adult life and when I did not I thought it was becasue I ate to many lobster tails.  NOBODY with a healthy and otherwise normal homeostasis who goes to see their primary care is going to be give the not so cheap blood test for HCV.  Your ridiculous, do you even see the irony of what you have written.  Did you have a HCV test when you were 20?  boy your a miracle child ....not

do not infer or write that I do not have a complete understanding of MY illness.  I DO.  I also love health science and your full of baloney.  

I do not know which is more ridiculous the statement you made about the pharmacuticals companies or the 1.8 infection rate.  tell me which state in this country does HCV as a standard part of blood work ups, without the client identifying a reason, tell me how many graduates from college getting started in their field or poor little rich kids who go to the doctor tell them HCV I have made some bad choies while having a great time?????

I am not going to "edit" this I may have rattled on to much or repeated or gotten off point and the list is long, but your full of it.  and if there is one thing I can understand and PROCESS it's that fact.  

the current "treatment" is great for acute cases, however the truth is if you have had the virus for say 30 years and have have underlying other health issues and MANY people in their 50's do or have developed hyper-tension, Type 2 diab, gastrointestinal issues,heck theres one for evey oran system my point is the immune system surpression while carrying this virus known or unknown is affected and therefore you treat with peg and ribo and those other issues are exasserbated or even worse disease develops in that system.

go fly a kite or tell me you read text books and not pharmacutical pamplets and internet hogwash.

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You dont take any Sh1t do Ya.
FYI in Aust the rate of diagnosed HepC cases is 11,000 per year. These are documented actual cases not estimates. The estimated rate is 16,000. I'll let you and MrLiver decide if the US with a population 15 times that of Aust only has double the rate of new HepC cases per year.
CS
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today...you have brought tears to my eyes.

by prompting me to look at the immune system,chronic hcv, and the inflammatory response you have not only re focused my attention but also filled in many gaps in my understanding!

your discusssion on eubiosis, fibrosis, metabolic stressors,anti oxidants, chronic disease may well have changed my life as well as provide me with valuable insights to share with others with chronic/ acute diseases and the inflammatory immune response. interesting, a critical care conference i attended this years focus was on inflammation. but i did not come away from the conference with near the understanding that you have evoked by your discussions but i can see how valuable it will be in my field of nursing practice.

i am on TNF inhibitors resulting from an auto immune arthropathy i developed some 20 yrs after chronic hcv. i have struggled to put this condition in perspective and have questioned every doc i know about it. (as i have no genetic predisposition). i thought for some time the chronic hcv  causing an immune imbalance was a culprit in the development of this auto immune disease. it is not until now that i realize a more complete explanantion may be found by examining your excellent observations and provocations. i specifically asked my rheumy (who tells me he is an expert on the immune system) for measures i can take to decrease the inflammatory response causing immunopathology and progressive damage to my joints and soft tissues.  he smiled when i brought up the anti-inflammatory diet i discovered with no comment pro or con but only to comment i need to take my prescribed meds.  thanks to you i may be able to put together a regime of supplements that may well be useful to achieve a remission and who knows perhaps even come off the TNF meds.

although at present i am not able to have an intelligent dialogue with you and explore your expertises give me some time to review and reference my studies.

thanks can hardly describe the feelings inside my heart at this moment of discovery you have stimulated for me. so now i will dubb you "SIR SAINT HR"
hugs xoxoxoxoxoxoxooxo
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ok i will try to put this together in reponse to your questions

Q- "the importance of preventing leaky gut syndrome"
A- the largest part of the immune system is in the mucosal lining of the gut. the immune system makes sure undesirable elements from digestion do not get into the bloodstream. when the intestines become damaged its creates a hyperpermeable state in the mucosal lining and allows the putrefaction and release of injurious toxins and pathogens to be released inot the blood stream. this process creates stress on the immune system to stop these toxins migrating through the body.
the immune system depending on the state of intestinal leak may become overworked and the toxins then may become settled into different tissues and organs of the body creating a new problem. INFLAMMATION.

the added toxic waste material is transported directly to the liver through the portal circulation. although the liver has a certain degree of imuno tolerance it must now work harder to detoxify these products. in a healthy liver and intestine the liver is able to easily perform this amazing process. but in the advent of leaky gut and chronic hepatitis the liver and the immune system may soon become unable to meet the metabolic demands of the circulating toxic loads.  as the liver becomes overwelmed (due to chronic viral infection or other metabolic diseases) the immune system/ inflammatory response is stimulated and the result is activation of liver macrophages and kupfer cells and the construct of fibrosis.

prevention of leaking gut may be achieved by a process of eubiosis or by keeping healthy bacteria in the intestinal tract.  this may be accomplished by diet, lifestyle changes (ie stop smoking or exposure of environmental toxins), stress relief, supplements ie probiotics and digestive enzymes,  recognition of medication induced imbalances, and replacement of underlying deficiencies. also the therapeutic effects of flavonoids (natural anti-inflammatories) and  some neutraceuticals also promote digestive/liver  health by their anti oxidant properties to aid in the metabolism of products of digestion of proteins, fats and carbohydrates. especially lipid peroxidation and promote the synthesization of glutathione(one of the bodies most natural anti oxidant and detoxifier. thus free the burden and stress on the immune system that will be more equiped to handle the release of endotoxin byproducts released by basteria and pathogens into the blood stream causing inflammation liver stress and in severe cases sepsis leading to organ distress, and failure.

Q- "in what way can NAC impact the pathway of LPS."
A- by improving metabolism, cellular function, stabilization of cellular membranes and replenish
deficiencies of certain immune cells such as T- lymphocytes. there are more specific benefits of NAC but as a liver protectant it is highly therapeutic.

btw....just to share a case that came to me as i was talking about this.
i recently has a 45 y/o m, in my unit with pneumonia/sepsis induced ARDS. after 2 weeks of a massive arsenal of antibiotics, and ventilatory support he was not responding to efforts to be weaned off the ventilator. inflammation was running a rampant course in his lungs. one night it took me 35 grueling and heart throbbing minutes to break up a mucous plug in his endotracheal tube. finally a doc responded to my frantic calls and came and re intubated him. at this time i asked him for an order for muco myst to prevent mucous buildup in the respiratory tract and ETT again.  now you have to remember he failed weaning trails for over 1 week prior to this incident.
within 5 dyas of muco myst delivered nebulizer treatments he was able to be successfully weaned off the ventilator. OMG!!!!!! i am now even more amazed to consider the therapeutic effects of the NAC. i only wish i could of been present in his rehabilitation to give nutritional education and discusss the benefits of supplementation.

again thanks Sir HR. this is only the tip of my ice berg of exciting research to explore
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Heading off to take my NAC. Thanks.

Nic Nac paddy wack throw your liver a bone. . . . .
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LOL you are funny!
serious i hope and encourage ALL to really read HR comments about preservation of liver histology. especially the ones paying beaucoup monies for herbal remedies that they are trusting natropaths to prescribe for them. this info may create a meaningful dialogue with your docs and help you take the quack out of alot of ducks out there ;)
it may be one of the best things you do to help your liver!
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Must be careful with NAC though because it  can eventually become a pro-oxidant over time once a persons reserves are built back up.  A more safe way to build glutathione levels(nac's main job) is by daily intake of 1-3 grams of vitamin c or lipoic acid.
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funny now how my mind is swirling with past experiences that connect to your promptings.

a few years ago my prized show horse developed a colic due to intestinal impaction. (somewhat related to constipation but worse in the equine species.)  for 26 hours we fought to restore intestinal function and my vet did a few gastric lavages, administration of antibiotics, and intavenous fluid support. by the 40 something hour my horse died (one of the most grievous times in my life) due to what the vet described as endotoxemia. this was also confirmed post mortum.
now i wonder........if we could of administered N acetyl cyteine iv if my horse could of has a better chance of survival?(as the impaction had already to break up).  when faced with mortality this may be a useful adjunct?  although it is not used in human sepsis on my unit i will ask our resident intensivist for more info.  but my vet might be willing for a try the next time i am in this situation?

interesting NAC also may help prevent influenza infection and reduce flu symptoms. perhaps this is achieved by not only breaking up respiratory mucous, but promote cell homeostasis in the respiratory tract,  with its added beneficial effects on the immune system etc... good news for us going into flu season?
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Hi sparrow

the statistical stuff was just bunk, I could not stop myself.  I worked in emergency care and saw a large percentage of at risk behaviors that resulted in injury and emergency care.  The numbers are low of these young adults that were tested for hepatitis.  therefore for a 1.8 percent number to be put in writing "as if" it were factual is ludacrist.  I should not have said moron, I'm ashamed of myself for that.  I feel in so many ways that these inflated and inacurate numbers are as big a part of the problem as the disease itself.  

It's like MRSA used to be in the hospital or nusing home rehab setting, now it's moving into our children, all because of a simple task that even the lowest paid health care worker learns  from day one....wash your hands...change your gloves.  In the big scheme of things if you have the ability to understand what these percents that are so ridiculous are as bad as not following universal precautions.  It sends out a message that is incorrect, just like that message so many people go into a hospital with...they will not be given anything they did not come in with, they are safe.  

I should not have said moron, I am sorry for that, and my tone is like a bad meal.  

As you must know from experience documented and estimated numbers are never even close.  estimated is always off by a large number.  diagnosed is what it is, but I would love to know the age range of these 11k diagnosed.  I believe in my heart it has such a big connection.  and I would wage there were 11k in a younger age range that have the virus today and are not diagnosed.  So how can we get healthcare to routinely start doing not only HIV testing but HCV testing?  that would change Mr Livers numbers over night.
oh and how many HIV people have undiagnosed HCV, those would bump up the number also.  Many HIV people have hepatitis for years and do not know.

Cool and sunny here hope your sky is blue also
Lanier

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thanks, yes a very good point.  i will continue to explore therapeutic doses and toxicites.

btw, a article i read stated 1200mg/day for flu......but again as i am not sure of therapeutic dose ranges and serum levels, and length of treatments in an acute situation. i need more time to explore this more.  do we need to make sure we supplement with vit c and other trace minerals if taking?

i will go back a re read HR's comments on PPC as it may be the safest when looking at a liver health supplementation program.

please all do not take my ramblings as any verdict of what is best for you or certainly rush out and buy NAC!  i am just beginning to put this information together. safety  is to be the NUMBER ONE consideration before implementing any supplement.  from HR's information on PPC this might well be that. for sure we need to run by any supplementation program with our hepatologist before starting.
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HI.
intersting post and LOL i just have to get off this computer for awhile.

in my place of work i have taken the logo of "liver angel" by this title i encourage all to be screened for hepatitis especially if in the health care industry. we certainly can take alot of the unknown's out of the population by testing and educating the risk factors where testing would be  more important.
i bet you have red and golden wings also!

hugs   stay well :)
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"Must be careful with NAC though because it  can eventually become a pro-oxidant over time once a persons reserves are built back up.  A more safe way to build glutathione levels(nac's main job) is by daily intake of 1-3 grams of vitamin c or lipoic acid. "

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I've been taking time--released vitamin C (4 grams a day) for the last 20 years religioiusly. I better watch my NAC intake, no?

I swear by Alacer Supergram IIIs. The guy that discovered vitamin C and the guy that discovered vitamin B-5 used to work for them. The theory is that vitamin C doesn't work unless on time release and normal C (acetic acid) has a pH too low for the intestines to handle. So. . . .by combining with a potassium molecule the C becomes neutral and thus can be more effective as time release. There is also a slew of B-complex in the Supergram IIIs. My stress and memory really are grateful. Now I'm thinking my liver is too!!
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Thank you for your kindness.  I am so happy you are working, I miss the field so much.

I have a sister who went the other direction in life and was a homepathic professional.  she had a health food store, and a reflexologist and visits from a irradologist on a scheduled basis.  It is amazing to me that way back when I was in clinical medicine and healthy any young professional should be, the irradologist told me I have liver flukes and needed to investigate my liver health and function.  that was in the early 90's and I laughed it off, same message came from the reflexologist about my immune system and liver function.  It was so asstounding to think about now, back then my sis packed me off home with a suitcase full of liver cleanses and supplements.  I drank the teas and took the tablets because I felt they could not hurt me, but had not doubt I did not need them.  On one visit she had a person their who read "colors or auras" I remember she said I was blue so maybe that is what you mean.  I was born in March and always have been a sucker for the needy and also blue is my favorite color so I laughed about that one too.

Life is such a journey.  Now days I think anybody might just have the answer and clinical is not the only road by a long shot.

thank you for not thinking I am a creep or mean person, I am not.  I want everyone to get well here.
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"Life is such a journey"  
yes it is...especially with hcv taking you on a few unplanned detours!
my that an interesting story. does your sis still have her health food store?
perhaps some of the interesting information taught by HR will be able to help you. it sure wets my appetite to understand the science behind it in my very best limited way and make a plan to promote the best health possible considering my immune sytem is shockingly shot at present.
well sweetie and sister of the white hat ya ya matching stockings ho. my professional love and best regards to you in THE H journey. we all need to laugh a little, cry a little, and most of all search
a little along the way. thats the story of.....
hugs
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Honestly, I don't know where to start with your rant. There are so many errors of fact that it would require more time than I'm willing to spend on someone who thinks they have it all figured out. However, from from your posts I think it can be safely determined that you don't know much about HCV at all.Your rambling diatribe didn't contain one cogent thought and was riddled with factual errors .

All of my numbers are valid. All of the countries on earth who have determined their population's infection rates on every disease do so based on statistical modeling. Every one of them is wrong and you are right. lol   So, pray tell, just WHAT is the infection rate in the U.S. for HCV if its not 1.8% ?  And guess what---the infection rate for health care workers in the US is also 1.8 %. No different than the general population. I'm predicting right now that you won't be able to wrap your head around that one. Many people are walking around with heart disease and don't know it, yet the CDC ,for example, can give a very good estimate for how many people total in the US are afflicted. How is that done ?

People like you condemn any numbers reached by statisticians simply because they do not understand statistical modeling and the various formulas used to determine such numbers. It is an arrogant position to take when you think something is in error simply because you can't figure it out on your own has it was done.

The antibody test for HCV is relatively inexpensive. Another of many incorrect statements you made. At the yearly health fairs throughout the state I'm in the test is offered for $10. Most people can afford tha,t but if not you can get a free home test or go to your county health service and get tested for free there as well. More doctors everyday are making HCV antibody tests a normal part of their patient's (we still call them that here because it fits the definition better than 'client') yearly physical exams---that's how I found out almost 8 years ago. I know many, many others who found out the same way.

You have mentioned your education and your job about 10 times now. I'm not sure if it is intended to impress, or you are offering it as an excuse for your lack of knowledge pertaining to all things HCV. If you really think those two things gives you some sort of advantage over others in the understanding of viral kinetics, epidemiology ,and the natural history of HCV- think again. Like I said your posts stand in testimony of just how little you know about the subject.
Even your speculations lack merit since you employ factual errors as the foundation and guiding light  behind them.

And I will repeat---no other disease has as many drugs in the pipeline as HCV does right now. What any individual pharm is doing has no bearing on that fact. I can point to at least 20 pharms that have their future vested in bringing an HCV therapy to market. People don't assume that type of risk because there is no money to be made.

We are discussing HCV which is not your disease alone. Its shared by nearly
5 million infected US citizens. And where have you been ? HCV has been recognized as a systemic, rather than  an organic disease, for many years now.

Does your anger stem from a failed treatment by any chance.? I've seen this happen before.

Not many people can squeeze so many inaccuracies into one post. You have a gift.

"your' a moron-----lololol----you should at least spell the words right if you are going to call someone a moron.

If you want it, you can have the last word as I see no reason to continue with this exchange.
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Thanks for your reply. I want to further explore this BBC story--I just found some of the research info last night and really haven't had any time to digest it.
I kinda got sidetracked and to be honest I haven't devoted much daydreaming time to the topic yet. I would like to look into a couple of things that I'm not totally clear on, to see if my initial thoughts (speculations) have a comfortable amount of science behind them. I know there are many viruses that employ a CTC transfer of virions and I know it would be helpful to me to review the known and/or suspected methods used by the other viruses for CTC transfer. I think the discovery is interesting-- I guess I'll probably start with trying to ascertain if this mode of transmission has any clear benefit to the virus. I need to read all of the comments posted above---I briefly read a few of yours that addressed this question of benefit and a few other people's and thought many were intriguing.
regards,
Mr Liver
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no lets play some more. and I spelled it wrong because I never speak in such a way, I was wrong too.  HOWEVER it still does not change my perspective.  AND I do not care about education I could care less.

So your saying this 1.8 number is including all the diagnosed and not yet diagnosed HCV people ?

would you be willing to include the "possible" variance, you know like in all the other great "polls" and statistical guesses we have.  lets see an average is 7-10% error one way or the other.  how many "healthfares" would you say you go to in a year and sell these 10.00 kits?  and how many people buy them?  that would be interesting to read.  And if it is 10.00 why were we not doing it in the emergency room for the 20 years I was there?  

I have not "failed" anything I am still here and moving right along.  just because I do not accept your pharmacutical packet sales pitches.  what exactly have you "seen"  
and what is your gaggle and systemic and organic?  

and point to 5 of these pharmacutical companies please?

are you in politics or related to hilary clinton? your "more doctors everyday" is a political pile of ****, they do not have your 10.00 test at the primary care, or am I wrong there too?

and if these little "health fair dream test: NOT ANTIBODY OR SURFACE ANTIGEN" are  EVERYWHERE
why don't our primary care doctors use them???
why Labcorp would be thrilled...

why don't we just have "HEALTH FAIRS" AND COUNTY FAIRS AND SELL ELEPHANT EARS AND SIDE BY SIDE.  explain to me when I had my hepatitis titers for clinicals the test I did take at the local health department (becasue I was a poor college student) came back fine and off I went into the hospital.

we are writing about 2 differnt tests here rocket man.  I am NOT speaking on ANTIBODY TESTING in a 10.00 kit or at the health department and I live in florida and I know hundreds of doctors and I know of NOT ONE WHO DOES HCV testing as a standard blood work up. of any kind for an elevated liver enzyme unless the client identifies a reason or is going into the EMT program.  healthcare workers would have a higer %%%% of having this test at the doctor (not the fair) than any other group.  I have many freinds who have elevated liver enyzmes, air traffic controllers, lawyers, accountants, real estates people and they have other issues hyper tension yada yada yada, and NOT one has had any HCV testing done PERIOD.  so what is the criteria >>>>

and are you suggesting we all go to the health fair if we suspect we have HCV, but what if we feel fine or what if we think its a joke, and would rather check our blood pressure at CVS and buy our "kits' there with our malox.  I am laughing now.  

go into ploitics even if your a dishwasher your a natural.  you have the gift of B/S statistics and polls and health fairs are way better than anything concrete.  

be sure to post those pharmacutical companies I have 3 girlfriends who are reps and I would love to let them in on the secret.  how much money in dollars would you say is shot over to the HCV researh labs every year?  have you got the stats on that?  and is it more than erectile dysfunctions? is it more than diabetes?  is it more than colon cancer?  is it more than HIV? is it more than heart disease? is it more than Alzheimer's?  where is it on the list ?  look way, way, way down and cite me the dollars not the little companies on the NYSE that are trying **** that is going nowhere fast.  

I am familiar with the CDC I have been to meetings in Atlanta and I am going to look into you 1.8 numbers and the correct information to go along with it.   it the only valid place you have cited, in fact it is the ONLY name you have used for any of your gaggle or reflux.

Lanier

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here here! i second this discussion and return to the original intention of the post.

in reviewing immune response and CTC transfer i will take a guess that perhaps the only benefit of this transfer to the virus is that it will escape the adaptive immune response (specific primed Tcells of viral epitopes, formation of new antibodies, stimulation of further specialized T-cells, and throw another monkey wrench into research trying to develop an vaccine. i am also in suspicion that CTC infection might infer a greater advantage in the viral envelope proteins to lock onto the cell surface in a way to further disarm the immune system?
perhaps also this is an viral survival techinque to preserve its host cell?

however the cellular innate response will be there to give a fight but probably unsuccessfully as it was designed to work with the adaptive or humoral response in viral infection.

i really liked HR analogy to describe the process of reinfection vs elimination of the virus intracellularly.  this has got to be a classic!
"it is the difference of fire spreading house to house or being spread all over the city by trucks using the streets throwing our burning ambers or by tornado winds"
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please share the site of this BBC article as ron did not in his post.
thanks
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I just read your post here, got so wrapped up with defending my opinions I admit I had not, I understand the histological orginazation of the liver and what your writing here is really good information I am speaking to the post from 11/14/07

I should have read it before the others and then we might have more common ground.  Mr liver and I will never be anywhere on the same solar system but your kuffer information is right on target.

lanier
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"Number of new infections per year has declined from an
average of 240,000 in the 1980s to about 26,000 in 2004"----www.cdc.gov.

I'm doing the math....dang ! I said an 85% reduction in my earlier post and guess what ? It's even MORE than that.

You inferred that my claim the least. There are  a multitude of reasons to explain the differences in infection rates between countries.
http://www.pubmedcentral.nih.gov/articlerender.fcgi?&pubmedid=16614741



The case presented in the abstract I read did not show any data showing that the relapse didn't actually occur between the time period leading between EOT PCR and the PCR which was administered after EOT for his lymphoma, many months later. Furthermore, there is no evidence that would eliminate the possibility of re-infection before the last PCR was taken, as well.There would have been plenty of time in between PCR' s for this to have happened although I'll say that the odds would be extremely low for this to have occurred, yet entirely possible.  Even if the relapse was genuine it was not beyond 24 months. So, once again an unverifiable claim has been given.

" Swain et al reported that in only seven out of 845 patients who had been successfully treated with interferon monotherapy or combination therapy HCVRNA was detected after 391- 1076 days off treatment ( 20 )."

This presents zero data to confirm that the relapses didn't occur well before testing was done post-SVR. And no mention of how often tests were peformed. Even if they were every 6 months this allows time for re-infection to possibly take place. Obviously, this is not a well-documented claim.

"In a recently published study no recurrence of HCV infection was seen in any patient from a total of 187 HCV patients with SVR after a median follow up time of 29 months (range 12-172). Three out of 187 patients in this study had transiently borderline positive HCVRNA once within the follow up period but it was negative in subsequent examinations and no patient developed hepatitis. "

This part of the abstract showed  NO RELAPSE in this study of 187 patients tested at a mean avg of 29 months from EOT. This was in the SAME abstract, yet no mention of it in your post for some reason.

"but I am sure I have come across the same only it was 7or 8 years after SVR"  -
If you are sure of yourself then present the study. If you saw it on the internet I'm sure it still exists. To be honest I would think finding a >2 year post-SVR relapse would be much easier than finding an 8 year case of it. Perhaps its in Medline, Elselvier, Wiley, Pubmed, CDC, NIDDK,NIH,or maybe in some of the journals like Hepatology, Gastroenterology Today, Virology, etc etc. All searchable for those who want to take the time and learn.

Do you think I have nothing better to do than hang out on the web and make up phony numbers so I can post them on a support forum to misinform or mislead ??? Exactly WHAT would be the point in that ??? I can assure you Cocksparrow if I post a statistic I CAN back it up. I don't pull imaginary numbers out of thin air, unlike some. And I don't cherry pick paragraphs out of
abstracts in an attempt to bolster my claims.

And if you have a problem with anything I say related to HCV in the future why don't you just address ME about it ? You don't have the cajones or what?



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Just to chime in my two cents:  I do not personally believe that 'relapse' is the issue when we discuss the 'viral persistence after SVR ' found by a number of researchers over the past few years.  When this virus is successfully treated, it may well go into a tightly controlled remission, which is almost impossible to overcome.  In other words, no relapse, but possibly also not total and complete eradication., I can't support the potential for the virus to remain at sub-detyectable levels after SVR because I don't do the research.  But I can read the research, and clearly there is something causing quite a bit of interest, which is being identified in the PBMC's, liver tissues, and other organs after applying higher than normal amplification in testing.  If there were no issue here, none of us would even be discussing the potential for viral persistence.  If you look above, HR also posits that this phenomenon may well be valid.  I thought that most of the board contributors had discussed this issue ad nauseum over the past year or so.

My point is this:  Yes you are correct, we are essentially "cured", but that does not automatically presume or prove that there is no dormant, or 'controlled' virus left in the body.  This concept does not really bother me,and does not seem hard to believe.  The concept of a virus being placed into a more or less 'permanent' dormant state is just as likely as the virus being absolutely eradicated.  I do believe that many prominent researchers from all around the world have come to similar conclusions.  Or at least that is how I read their discussions.  

DoubleDose
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Written Testimony of Bruce R. Bacon, MD, presented to the House Appropriations Committee, Subcommittee on Labor-HHS-Education April 29, 2004, Washington, DC
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Written Testimony of Bruce R. Bacon, MD, presented to the House Appropriations Committee, Subcommittee on Labor-HHS-Education April 29, 2004, Washington, DC
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Mr. Chairman, I would like to thank you for the opportunity to present written testimony to the Subcommittee on Labor-Health and Human Services-Education and Related Agencies of the House Committee on Appropriations.

My name is Dr. Bruce R. Bacon and I am testifying before the subcommittee in my capacity as the President of the American Association for the Study of Liver Diseases (AASLD).

AASLD represents more than 2,800 physicians, researchers and allied hepatology health professionals. Throughout the Association’s 50+ year history, the members have been committed to its vision and mission and have strived to achieve the goals, objectives and principles set forth by the leadership. For generations, AASLD and its members have been a catalyst for the investigation and treatment of liver diseases. AASLD upholds the standards of the profession and fosters research that generates improved treatment options for the millions of patients with liver disease.


I would like to discuss with you the funding issues related to the National Institutes of Health, the Centers for Disease Control and Prevention, and the Health Resources and Services Administration. I would also like to discuss the fiscal needs created by the passage of HR 3926, the Organ Donation and Recovery Act, which was recently signed into law by President Bush.

National Institutes of Health

Mr. Chairman, the AASLD fully understands that incredibly difficult dilemma that faces this committee. We look at it as a classic situation of supply and demand – the demands for funding that you are receiving from groups like ours far outstrips the supply of funds that you are likely to have available when the Appropriations Committee divides up the available resources later this spring.

We are fully confident that the committee and the subcommittee will carefully consider these competing issues and will endeavor to establish priorities that reflect the best interests of the American people, no matter how difficult that challenge may be. It is for this reason that we feel secure in joining with our colleagues in the health research community in seeking an 8 to 10 percent increase for funding for the NIH in the FY05 Labor-HHS bill.

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Within the NIH, Mr. Chairman, liver disease research takes place in more than a dozen different institutes. However, the largest volume of research occurs in NIDDK, NCI, NIAID and NIAAA. With your permission, I would like to take a few minutes to discuss this important work and some of the challenges that continue to confront researchers.

Because the liver is part of the body’s digestive system, the NIDDK is the lead institute for liver-related research. Their focus is on the impact of various diseases and conditions on the organ itself. Much of the work that NIDDK does in its intramural program and funds in its extramural program is related to diseases like hepatitis (particularly A, B and C), acute liver failure, and fatty liver diseases (including non-alcoholic steatohepatitis or NASH), as well as research related to transplantation. While fatty liver diseases are not as well known as the various hepatitities, they are important co-factors with such critical disorders as diabetes and obesity.

Hepatitis C is a particularly vexing problem. Mr. Chairman, approximately four million Americans have been infected by the hepatitis C virus (HCV) and nearly three million of them are chronically infected. However, most do not know it. Because HCV infection can be asymptomatic for more than 20 years, most persons suffering from hepatitis C do not discover it until their liver is virtually destroyed by the virus.

For this reason, hepatitis C has become the largest cause of liver transplantation in this country. Given the incredible shortage of organs and the number of deaths that occur while persons are waiting for a liver transplant, research into early diagnosis and improved treatments of hepatitis C is essential for the well being of our patients.

NIAID also has an important role to play with regard to hepatitis C. This is the lead institute with regard to the development of a vaccine. While the spread of hepatitis C has slowed as a result of improved testing of the blood supply, new cases continue to be diagnosed, at a rate of about 20,000 per year.

Unlike hepatitis A and hepatitis B, there currently is no vaccine for dealing with hepatitis C. NIAID is funding research in this area and a small human trial of an experimental vaccine is underway. This could represent a substantial breakthrough in stopping the further spread of the disease.

Mr. Chairman, on another topic, the number of persons who develop and die from liver cancer is increasing, with 24 percent more cases diagnosed since 2000. This is in stark contrast to many other kinds of cancer, which are actually decreasing in incidence and in deaths. This month, NCI is holding an experts conference, along with NIDDK, to help define the most urgent areas requiring additional research, professional education and public awareness initiatives. AASLD believes it is essential that NCI, working with NIDDK, follow this conference with the development of an aggressive and targeted research portfolio, using all available mechanisms of program announcements, requests for applications, center grants, training grants and more.

Centers for Disease Control and Prevention

Mr. Chairman, the Centers for Disease Control and Prevention (CDC) also plays an important role with regard to the public health impact of viral hepatitis, especially hepatitis C. Within the Center for Infectious Disease, the Division of Viral Hepatitis’s National Hepatitis C Prevention Strategy is a key program that assists state health departments and voluntary health organizations to provide testing, counseling, outreach and referrals. It is critical that this program receive significant funding increases to begin to come to grips with this epidemic.

As I mentioned earlier, most persons suffering from hepatitis C do not know it. An aggressive campaign of physician education and public awareness is needed to bring a focus on this disease. Early diagnosis and treatment may be the best defense we have at this time against liver damage, the need for a transplant, and eventual death from liver disease.

Health Resources and Services Administration

Mr. Chairman, the Administration’s budget has again requested $25.0 million for the organ transplant related activities of the Health Resources and Services Administration. These funds support a scientific registry of organ transplant recipients, as well as the Organ Procurement and Transplantation Network (OPTN) to match donors and potential recipients. A small amount of the funds are used for public education and to support agency staff, which provides a clearinghouse and technical assistance.




rock on
Lanier
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CDC IS FLUSH WITH CASH....NOT.  your 1.8 number comes from a dieticians research study how far of the mark could that be...on just about as much as your ridiculous statement of hundreds of pharmacutical companies beating down the doors to research this virus. BUNK.

Maybe the penny stocks on the NYSE are what your using for this data. who knows.  I agree now I have no need to discuss anything with you again.  dieticans and penny stocks are not my field.

rock on your a legend in your own mind
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"on just about as much as your ridiculous statement of hundreds of pharmacutical companies beating down the doors to research this virus".
I don't understand most of this thread, and probably be no better off if I did. But this comment is unfair. We are very very lucky to have a disease that is common. There is money in this disease, so there is research occuring. If we had some uncommon, as many people do, there is just often not the money to commercialize potential drugs.
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In the big picutre HCV is not getting it's fair share of dollars.  the statement you qoute is out of context.  Mr liver and I have been debating this.  I never said there was NO research, but I can tell you in the past ten years there were more dollars that is what I am talking about spent of erectile dysfunction than HCV.  and since I have no penis I feel like I got the "shaft"  

I don't want to argue the point anymore you guys are sold that HCv is just the cats meow when it comes to research so dream on.

I did not mean to offend you, but if I did life goes on for us both it really is no big deal, this is a BLOG
I thought people were "allowed" to share there knowledge and not have to fight for a different idea?  I am not right about anything heck I am wrong all the time I am human, I don't want a blue ribbon.  I just know what I know from where I have been.

have a nice day go Packers and crown 24 king

Lanier
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sorry this is going to take me a long time to read through,

but a dumb question, regarding thick protein shells you said

>>>>>>>>>>>>>>>The virus manages this extremely critical  “escape from neutralizing antibody” feature by having evolved such a surface coat of proteins that it has enough lipophilic amino acid residues placed at strategic points as to bind circulating lipids, that give it a secondary, soft coat, that prevents the antibodies to reach the epitopes and hence effective, strong binding.

ok so help me understand, if more lipid protects the HCV from the antibodies being reached by the eritopes, then why would adding PPC to the health.meds regime not aide the virus as well by giving it extra protection?

I may be misunderstanding something here, granted, but with my limited knowledge of your lingo, it's kinda hard to be sure if this new info does damage to the PPC equation.
thanks
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All I have to say about your rants is to repost why HepC is called the Dragon.
The liver is represented by a dragon and is said to store anger.

Certainly applies to you
Have a Nice Day
CS
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as usual as i reread HR comments i find a new gems to explore

your question stimulated this re read. although your inquiry was about PPC in relationship to circulating lipids i found something more remakable from his explanation.

i would guess that PPC has no effect to increase the development of the secondary lipid envelope coat of hcv because 1- PCC composed primarily of polyunsaturated fats actually decrease plasma triglycerides and cholesterol. 2- the addition of polyunsaturated fats in circulating plasma would not have any effect in the ability of the lipid envelope layer of hcv binding to plasma circulating lipids.
will be nice if HR comes in to elaborate! would be nice to clarify if the virus binds circulating HDL's or LDL's in plasma?

but even more remarkable in his explanation was the statement that hcv envelope proteins  bind to circulating lipids thus giving it that soft coat that interferes with antibody attachment to the viral epitope. in effect preventing the ability of the antibody from processing the viral epitope and neutralizing it.

wow! i thought antibodies were ineffective because of the envelope proteins E1E2 especially E2(envelope proteins) are hypervariable thus preventing effective antibodies forming due to the constant development of variable epitopes. (the genetic drift causing mutation and development of quasi species cause the hypervariability that are capable of neutralizing antibodies).

i never considered that the lipid layer on the envelope would also prevent antibodies from forming a strong bond to the viral epitope!  wow wow. this is the firist time i considered this aspect.

also i never understood the lipid coat to be able to attach more lipids when circulating in plasma. i always thought the bi layer lipid coat was formed from intracellular lipids during the virion maturation inside the cell and by the process of exocytosis. interesting now to realize the viron has the ability to attach circulating lipids in its defense system.

now my coggs are spinning lol!
i came across an interesting article about an emerging science in viral immunotherapy whose focus is to develop agents that will remove the lipid viral coat (delipidation) thus increase viral antigen presentation and processing.  
site     http://sec.edgar-online.com/2006/03/15/0001047469-06-003438/section2.asp
would love HR to comment on delipidation as a prospect to aid the development of an effective vaccine.

also one of my fav sites on hcv viral biology is
www.natap-org/2001/jun/MoleBio.PDF
i have lots more of such if you are interested

another insight in to the way the virus evades the adaptive (humoral) branch of the immune system!
thanks merry....i enjoy your comments and posts! our understanding is alike a baby compared to HR but perhaps together we babies can reach better understandings of chronic hcv
hugs
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clarification of above.

it is the proteins on the lipid envelope that attach to circulating lipids. as there are only 2 main envelope proteins on the hcv- E1 and E2. i wonder if both or one has this ability?
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Since you seem to be getting off on the lipid-confounding-antibody groove, you might find the study referenced below interesting reading. Basically it states that high levels of cholesterol, and specifically high levels of LDL (the "bad" cholesterol) were found to strongly correlate with RVR/EVR and eventual SVR. I actually employed this strategy during my treatment by loading up on the saturated fats prior to treatment and during treatment by eating lots of fattening foods (whole milk, pizza, ice cream etc etc). Can't know if it helped, but based on the strongly correlative LDL->RVR/EVR/SVR data reported in this study, it just mighta!

http://www.natap.org/2006/HCV/080806_02.htm
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MerryBe

The virus manages this extremely critical  “escape from neutralizing antibody” feature by having evolved such a surface coat of proteins that it has enough lipophilic amino acid residues placed at strategic points as to bind circulating lipids, that give it a secondary, soft coat, that prevents the antibodies to reach the epitopes and hence effective, strong binding.

ok so help me understand, if more lipid protects the HCV from the antibodies being reached by the eritopes, then why would adding PPC to the health.meds regime not aide the virus as well by giving it extra protection?

1. The antibody binding is already unable to prevent reinfection due to this mentioned feature, together with the constant adaptive evasion by mutation (correctly mentioned by whrose above , but left out in my earlier discussion so as to not further complicate the issue)  as part of the viral strategy to escape neutralization. Therefore, even if PPC would add to that " lipid coat" it would not matter. Once you are coated, you are coated.

2. The exact nature of these binding lipds is not known ( at least AFAIK). Chances are that the overall plasam lipid profile would not be altered by PPC so as to enhance this feature, even if  it would not alrready have maxed out .

3. There is a small component of neutralizing antibodies in place that seems to have some role in the ability to prevent reinfection in a setting, where there are only a few viruses trying to infect a virgin liver, like in the transplant setting.The HCIG experiments - passive immunization using plasma enriched for HCV antibodies in chimpasnzees- to prevent de novo infection-  had a small degree of efficiacy, but not enough to make the difference. But, as mentioned above,  Innogenetics in Belgium  is currently trying to develop two human monoclonals with the intenion to help prevent reinfection after transplant. I had a discussion in that specific regard with the two lead researchers actually working on this  at the Boston meeting, so I am up to speed on that approach.



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This is of course yet another twist to the HCV-lipid story. Since HCv seems  - among other attachment / transfer  receptors - to use the LDL receptor as anchoring/plasma membrane translocation enhancing mechanism, the protective effect of high LDL might be correlated to a competitive binding/blocking  of that receptor by high LDL levels, reducing reinfection efficacy.

Alternatively, high LDL levels may lead to "overlipidation/lovercoating" of the virions, where their trick starts to backfire, reducing attachment  efficiency at the hepatocyte membrane.

Please note that the HCV viral entry mechanims at present are only incompletely understood.
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haha ya, i admit i do get a kick over the "lipid confounding antibody groove"  

of course during my tx i did increase intake of fats ( with riba ) and in % TDI.  my geno 3a
pre -tx i had a lipid profile done and my LDL were abnormally low causing an alert for cardio vascular disease. this led to a full blown cardiac work up(all negative) and then an interest in dyslipidemia in chronic hcv.
material was hard to come by for this foray because of the lack of research on lipids and hcv.

from my limited understanding i thought that my LDL levels were somehow influenced by the virus perhaps causing the increase risk of steatosis (i did have this on BX). i got confused that othere however had higher levels of lipids with infection which then i assumed were related to diet and perhaps a hereditary influence. after tx my lipids all came back normal with perhaps a need to > HDL's in diet. i do enjoy my handful of almonds and walnuts daily.

the article referenced previously and others discussed the possibility of hcv using the LDL receptor to gain entrance in the cell. (one of many ways for cell entry) HR has it right on that the process of hcv entry into the cell are still not fully understood. i look forward to more coming as you know i am a "lipid nut" lol

back to using HR posts as a study stimulus....hugs HR... hope you are well!

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"loading up on saturated fats"
____________________________________
Outrageous! We get to increase the *HDZ factors and the **CG factors!



*Hagen Daz
**Cherry Garcia
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ROFL.  ha! i was thinking of asking HR to marry me but if you are serving hagen das, starbucks, and cherry garcia...maybe i will change my mind.....ahhh are you....
(of course i would have to leave the love of my life for 34 years)
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:-O
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What a thread! OOOOOOO Baby baby!
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I have trouble with processing in general,"  Andy, boy do we know that. My God even here you must give these people a hard time. You no nadda on HCV, as you drank all through your tx, and continue to do do. Please get help, contact your local AA.
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Please do not waste your time responding to Mr. Liver, who is also earthman, aka andy and an assortment of fake names.  He has very serious issues and has been shunned by other HCV forums.
Please keep an watchful eye on him, as he can be upsetting to people on tx.  I enjoyed your informative and was happy to see that you saw right through this nitwit.
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What a nice thing to know, I only came here I think around May-Aug this year.  I have never been on a blog or anything in the chatting, "im" video cam kind of stuff.  I was desperate, pitiful and still am in many ways.  Yhid forum has helped me.  I can vent and try to relatate to others like me.  I loved healthcare so much and miss the clinical setting and excitement, but I broke ranks years ago when it comes to Doctors, lawyers or Indian chiefs...lol   I was out spoken and asked questions about care plans long before I knew I was afflicted.  Now I am a ruthless advocate for people who need to be more proactive with their own health.  I wish we all could wake up well, I wish I could see my only child for 30 more years, inside my self awareness tells me it will never happen.  I just wish more people could get screened when acute.  they have made invto study this past January in a laboratory setting and so I am hopeful for those coming down the pike.  It's why I always  ask how old people here are?  (so rude)
anyway thank you again

regards
Lanier
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YOU ARE A KEEPER..
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DONT FORGET THE THE TRANSFAT BABEEE
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lanier: I can out pain-in-the-neck you anyday of the week

Xquizit: that is what is so crazy. They are saying that Riba stuff goes down better with a lot of fat. So . . . .once you are done with treatment you can sign up for a heart replacement
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hey, yer ruinin' all my dove bar moments....cut it out!!!!!!!!!
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thanks for pulling this thread up again, I was going crosseyed in the wee hours trying to finish readin it, then and hadn't gotten back to it....people do read, rest assured.
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whroose
thanks for that great response, and I need all the help I can get, so between the two or you, (HR) I'm getting the idea albeit slowly on some of this.
Just so you know, you're not a light weight, I'd not go there my friend, cause you are great

PS. I have all the autoimmune stuff you do, oiy, and a hornets nest in my liver this year, so it's hard to get caught up to speed in the middle of this horserace, so to speak,

but indulge me one more dumb question if you will:

and HR as well, or at least to ponder:

somewhere in here I think, Lord who knows where cause if life depended I probably couldn't recall enough of the wording to pull it up again with this search engines limitations,

, I seem to remember that the Riba worked by, in laymens terms, chopping up the RNA/DNA and thus interrupting the normally voracious replication aspects of the virus.

If this is not faulty memory on my part, then I would have to assume this means it get's done having penetrated the outer coat of the virus, sticky lipids or not, it has to get INTO the cell to effect the RNA strands before it can start chopping, and are these not inside the viral structure for the most part??  

If this is true then, that Riba has to get inside,
and then on the assumtion all cells are serviced to some degree by the bloodstream,
it means the Riba is getting around,
in which case whether the virus can do cell to cell transfer or not,
what real difference would that make assuming the saturation point of the Riba stays high enough? And, would not this somewhat explain then why the higher dosing seems to yield the more reliable results?

I mean since blood carries the Riba to every cell I'm just not sure the cell to cell replication is really a matter for alarm.

I did wonder a while back, could fat retain virus since it get's less blood supply proportionately,
also wondering could bone matter itself be a hiding place.

but ultimately my main question is, even given a circutous route through the circulation before a Riba molecule reaches a neighboring infected cell let's say,
won't each cell still ultimately get serviced with Riba soon enough....
and if often and long enough in duration then why would it matter so much???
And,  isn't that what the SOC is basically now proving out to a greater degree?
Isn't the longer duration tx resulting in people going UND for years now??

ok so that's not just one question....so much for my one time math major!!!!!!
: )))))))))))))))))))))
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oh my, LOL, your note reminded me of myself as i started to explore the incredible world of hcv.
one question leads to many others, time consuming to delete flaws in conclusions, time consuming to fill in the gaps of understanding. i am no expert by a long shot as i still have some big gaps, but time and persistance has been a friend along with many peers and their excellent discussions/debates and wisdom from experts like HR. another valuable base to focus study on is cell and viral biology along with the human immune function. lol a math degree may be challenged but certainly be an asset in comprehension on the molecular side of things!  then there is the school of hard knocks...sure to teach you some important lessons.

well to take on  the "Q"s as i can read em
CTC replication has No effect on ribavirin circulating and plasma levels, nor in riba's intracellular function.
the exact mechanism of ribavirin in the function of viral kinetics is still not well understood but some studies show it accelerates phase 2 fall in hcv rna.( very important to get that viral load down early in treatment for prediction of tx response).  the lethal mutagenesis effect of riba causing hcv error catastrophe only partially explains its effect on viral kinetics. as evidenced by ribavirin mono trials inability to reduce viral rna. there is a theory well described by a researcher called Sallie that explains the anti viral effects of ribavirin to be more due to replicative homeostasis as opposed to error castrophe. the article is tough reading though. (will give a link below).  riba also effects immune modulation and stimulation in concert with IFN synergistically, and that is why it not only functions importantly in the beginning to reduce viral loads but also to reduce relapse thus SVR rates. however as we know all genotypes are not created equal in terms of response to SOC. the reasons being not only host related but perhaps better explained by viral charactersitics.

high dose riba has its inherent risks not only with life threatening anemia but in renal impairment.
i am like many others impressed with some reports that state high dose riba (1600-4000 mg/day) changes SVR rate in geno 1 from 50% to 90%. however there are not enough studies to confirm or recommend this due to this dose is above recommendation and the associated SAE's.
our resident expert JIM can certainly give alot more info about this than i can.  so high dose riba may in this regard profoundly effect those early viral kinetics to favor rapid viral rna decline to achieve that undetected sooner (but only in combination with IFN) but as i said there are risks and one should only do this with the support of an experienced hepatologist.

when i did my treatment (geno3) i had a negative predictive factor of age and high viral load. i pushed for higher dose riba max wt based even though it has not been proven to increase SVR in my geno. however my doc agreed and by week 4 i was undetected. i personally believe the extra riba may have been a factor as my  pre-tx viral load was over 20 mill. for sure it did not hurt! although again with my geno a 4wk undetect is more likely the norm but relapse rate still not understood well. another reason i stayed on the wt based dose through out tx. btw i did SVR and for me my tx regimen was a success. would be interesting to compare me to me taking the 800mg recommended riba dose for my geno. i will never know this difference and glad of it.

so therapeutic or high dose riba has no relationship to CTC infectivity. you are right to conclude this.
longer duration in SOC has been shown to increase SVR in some response patterns such as relapse and partial responders.  i think this is due more to viral charactersitics/mutations that respond favorably to longer dose regimens.

in regards to fat or other organs where hcv hides. in my understanding hcv does not hide out in other organs, but has been proven to be able to replicate in other cells in the body outside the liver (its [liver] best and preferred medium for replicative success)perhaps thus providing a reservoir to some degree.  how this fact influences its ability to cause disease outside of the liver is still not well understood and debated. HR has explained the durabilty of SVR and this would support any reservoirs of virus out side the liver would not be disease causing once SVR is achieved.
it is known that hcv increases risk of lympoproliferative diseases and alters immune function(along with IFN) that may be the genesis for other immune related diseases. also Hr explained well the relationship of immune stress caused by inflammation especially with his leaky bowel pathogenesis of circulating immune complexes systemically as well as localy in the hepatocyte.  the evidence of its tropism has not proven to directly result in other diseases....but the jury may still be out in this regard as i understand it. without getting in occult virus which is another subject all together.

i hope this helps.. for sure HR and others can give alot more meat into your questions.
hope you are feeling well. sometimes study is a great way to divert anxiety. it sure helped mine although i am not as diligent as i was on treatment perhaps my understanding is improving without the effects of tx meds and SVR. some articles you may enjoy
http:www.medscape.com/viewarticle/543530   explains viral kinetics of riba and IFN
also http://www.virologyj.com/content/4/1/29    replicative homeostasis by Sallie good luck....it may take several readings to get his gist. however it is for sure a most excellent explanation and worth the study time to understand it.

hugs Whrose
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