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American Association For The Study of Liver Disease

<A HREF="http://www.medscape.com/viewarticle/495211/">ARTICLE</A>
Many subjects are addressed including 1)duration of treatment 2)marijuana and liver disease 3)persistance of virus after treatment. It's at www.medscape.com so you must be registered to view. Registration is free and well worth the time. Mike
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Avatar universal
I share your sentiments regarding tx, and concerns about loved ones, etc.  I also had a long tough time on tx, being sole provider for a family, a business owner, and also by necessity being involved in regular sports and school programs for the kids.  Faking it was often very difficult!

Please do bear in mind that my speculation is merely that....speculation!  I would like more than anything, to be totally wrong, as far as my concerns about HCV.  I think we need more research out there, and we need to have specific investigation of spouses and close relations to determine if there is any reproducing HCV in various tissues, other than the typical blood based testing.  They could conduct highly sensitive, amplified PCR testing on salivary tissues, sexual fluids/tissues, mucous membranes, etc. for several examples...in order to see if there is a problem.  My question is, why don't these very bright, highly educated scientists think to do this???

Also, another way to prove or disprove assumptions would be continued testing of SVR's for 'other organ replication', looking at them 3-5 years out from SVR.  Another would be testing FORMER spouses who are HCV-neg, but have not been tested for tissue based sensitivity in various organs.  Since the persons would not have had contact for years, it would be pretty compelling if they were able to harvest various HCV strands from the spouse who had not ever had HCV.

This sort of exploration would go a LONG way toward clarifying what we have on our hands, what the risks involve, and MIGHT explain the mysterious HCV cases with no known risk factors.

To be honest, I am shocked that the medical community has been so very slow to examine all these possibilities.

In the meantime, I will still remain optomistic that I am over-reading, jumping the gun, and being unduly paranoid.  I will hope that my logic is off-base, that my observations of familial symptoms have no relationship to HCV virus, and that I end up being flat out WRONG.  But I need evidence...We need PROOF.

Too much of the current research opens the door to all of these concerns!  They should finish the work, and issue a conclusive statement.

Heve a nice holiday, and enjoy the SVR.  I am receiving tremendous benefits from eradicating the blood/liver infection.  Let's pray that this is all there is to eradicate!!!!

DoubleDose
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Avatar universal
I appreciate the follow up articles and comments.  Now I don't feel as much the oddball 'alarmist' or naysayer that I fear I have recently sounded like.  The scientist in me, along with my own observations have led me to develop increasingly disturbing concerns about the 'entire' mechanism utilized by this virus, as well as the potential threat posed.  Here is some more of my thinking:

The people that we read about and know regarding HCV infection and treatment have generally acquired the virus through 'blood - blood contact of some sort...needle stick, drug use, surgery, transfusion, and related exposures.  THESE are the people with obvious HCV infection discovered either through liver abnormalities on testing, or, positive anti-HCV testing on routine blood testing.  This is the main population which we have been observing, studying, tx-ing, researching, etc. etc.

BUT, IF HCV is able to exist or reproduce in the lymphatic system, gastric mucosa, salivary glands, sexual mucosa, mucous membranes, THEN it is only sensible to assume that there may be a population out there who has ONLY been exposed through peripheral organs (NOT BLOOD).  This could include kissing, sexual contact, sharing anything with salivary contamination, contact with gastric fluids, etc.

Could this potentially infected population be harboring a low level, or localized form of HCV infection which does NOT show up in serum antibody testing.  Could this other sort of HCV infection be entirely 'missed' or invisible to the medical community (due to neg. anti HCV, and no liver involvement), BUT yet causing chronic illness within the host by direct infection of peripheral organs???  Eyes, oral mucosa, salivary glands,lymphatic, sexual organs, etc. etc.  This could remain isolated, or stay outside of the blood/liver, yet indeed cause a range of direct symptoms, and autoimmune responses as well!  You can carry out this chain of logic and see the various possibilities for a very 'different' breeding ground for HCV.  Could this long term, persistent infection eventually migrate into the bloodstream, after many years, thus emerging as full blown HCV serum/liver infection??? (all the HCV infections with no known cause!!!)

Current research is continuing to provoke my previously 'half-skeptical' concerns, and causing me to believe that we may be on the threshold of something entirely new...or heretofore undiscovered...and scary!

If the virus indeed replicates in these other cells (not just blood) than why shouldn't it be transmitting along those same lines????

This, of course, is coming from an SVR, who sometimes wishes he did not think so much, and would rather all this speculation be totally untrue.  But this is what I am beginning to suspect.

Doubledose
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Avatar universal
(another footnote regarding the importance of living well in the face of uncertainty). In the course of tracking down further work on  the <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15140984">cite </a>posted by Scott above, I ran into the following <a href="http://www.co-gastroenterology.com/pt/re/cogastro/abstract.00001574-200411000-00016.htm;jsessionid=BH9icqeeDBsofvyXV2L1pMHGc7kez43N1DbjbqluP1E80iUNDgyd!925374346!-949856032!9001!-1">review</a>. Published last month, this presumably marks the current state of the art regarding what we are and are not sure of. The last paragraph reads exactly like your posts above:
<i>"Intensive efforts are underway to identify
potential viral components important for its replication
cycle (protease, helicase, and polymerase) [4
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Avatar universal
I would get tested if I were you. Sexual transmission is not common but it does occur - I think it is about 2% to 3% chance of that happening. Play it safe and find out where you stand. Don't panic but don't put it off indefinitely either. Good luck.
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Avatar universal
this is biology after all, if different species can manage to exchange genes, passing a virus seems comparatively easy. The difference in the transmissibility of HBV vs HCV via kissing or sexual contact is really just a question of probability. Adopting too low a threshold on uncertainty could make life pretty hard. For example, what level of false positive/negative can you find acceptable on any given test result?
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Avatar universal
HI, MY HUSBAND JUST FOUND OUT HE HAS HEPC. HE WAS TOLD YEARS AGO HE HAD IT THEN ANOTHER DOCTOR SAID NO. THE DOCTOR HE GOES TO NOW DID EXTENSIVE BLOOD WORK AND TOLD HIM IT WAS ACTIVE.
THE DOCTOR WOULD LIKE ME TO BE TESTED. COMMENT?
THANKS, YOU SEEM TO HELP A LOT OF PEOPLE.
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Avatar universal
Weight has definitely become a big issue for me.  I can't seem to say NO.  I love good foods, bad foods (candy, cookies, chips, etc), and eat  much larger portions of everything since being off tx.  I have gained about 20 lbs. over my tx weight, and about ten over my normal.  Food certainly seems much more inviting now!

I keep meaning to set a real date, etched in stone, where I will begin a new exercise regime and go back to a healthy diet.  Probably Jan.1st will be my start.

The chest/throat congestion has reappeared for me as well since ending tx.  I have frequent throat clearing throughout the day, but especially in the morning.  Odd thing again, is that my wife and kids seem to now have the same chronic congestion, and a nasal inflammation/allergy that runs throughout the full calendar year.  It does not seem to respond either to antibiotics, or allergy related medications.  My antenna are up
regarding this symptom, as well as the dry irritated eyes, tinnitus, and frequent fatigue symptoms within my family
as well.  This is why I am concerned about all the 'other organ' research as relates to HCV infection.  The family members are all anti HCV negative...BUT????

Doubledose
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Avatar universal
<u>doubledose</u> - some thoughts on things you've raised:

1.) "<i>What would keep it from replicating in the organs of casual contacts, partners, close family members from things like kissing, sexual contact, etc??</i>". - This would seem to depend greatly upon the issue of transmisability. If we are talking about two differing levels of viral infection ('high-replicable' being the kind that produces global infection and 'low-replicable' being the kind that lingers without producing global infection), then there may also be differences in the transmisability of each type. Is it possible that low-rep infection is quantitatively too small to produce transmissible infection? I've seen a study suggesting that in high-rep infection, the greater quantity received upon initial infection (eg - from a direct IV injection full of virons versus, say, a needle stick) the quicker one becomes infected and the sooner one then passes from the acute to the chronic stage.

2.) "<i>IF infection can potentially transmit into peripheral organs in other people, would they necessarily have an HCV pos. response to standard serum HCV antibody tests???</i>". - I don't know how sensitive the Hep C antibody test is. If there is low-rep infection, would an equivalent low-level antibody response be enough to show up on current testing? "<i>(Why do the HCV antibodies NOT go away in SVR's???) Is the body still detecting HCV??</i>". - From what I understand, antibodies continue to stay within the system post-viral infection. For example, blood donation/collection agencies uses antibody testing (since it is the quickest and least expensive) as the first line of defense to turn away applicants that show up positve for Hep C antibodies, regardless of whether their bodies have cleared the virus (via SVR or spontaneously).

3.) "<i>ARE we yet totally sure that HCV is purely and only a blood transmitted virus???? ... Why Couldn't it transmit in those tissues? Or sexual mucosa???? Or mucous membranes..eyes..etc?</i>". - Is this possibly also a 'quantity' issue? I don't know if there are any Hep C viral quantity differences between serum and other bodily fluids and tissues. Does serum carry a quantity amount that can possibly replicate fast enough to get beyond the body's immune response, whereas these other fluids/tissues cannot?


<u>Bob L</u> - Good to see you. And great to hear that you've crossed the finish line and are already improving. I hope all continues to go well and that your tests results reflect the same.

May God's blessings and mercy be upon you.


TnHepGuy
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Avatar universal
I appreciate your responses to my questions.  You are thinking along the same lines that I am.  There may be differing quality and quantity of infection, according to the organ or tissue that it infects.  One might have rapidly replicating HCV infection in serum and liver, but the virus may only be capable of a lower level infection in the lymphatic system for example, or salivary system, gastric mucosa, sexual mucosa, eyes, etc.  

Maybe the multiple symptoms that we see in HCV patients are caused by DIRECT infection of the organ in question, NOT just some vague system-wide autoimmune response.

If this is the case, we have a bigger problem on our hands...
1.  For those who achieve SVR from blood and liver, is there a post-tx lingering infection in some patients, within other organs....and can this eventually cause reinfection many years down the road, given the right circumstances???

2.  How do we know that we are not infecting all those who we have sexual, or intimate contact with, within peripheral organs, thus setting them up with a lingering peripheral infection that might 'blossom' at some point in the future.  Note the Egyptian HCV studies showing an ever-increasing percentage of spousal positivity for HCV AFTER 20 to 25 years of marriage.  WHY the long delay?? (If HCV either infects the blood immediately or does not, as experts today believe)

3. What are the implications of long-term 'other-organ' infection with HCV, even if it is not present in the blood or liver?  Might it not already be 'out there' causing any number of unidentified syndromes like CFS, non-allergic rhinitis, sjogrens syndrome-like diseases, FM, lupus, etc?  If the peripheral infection of organs is sub-clinical enough to not provoke a major antibody response to HCV testing, then do we really understand the possible extent of the infection?

Note:  I continue to see odd, HCV-like symptoms in family members, especially spouse, and remember previous sexual partners showing several similar symptoms years ago.  Sx like dry eye, memory lapse, fatigue, odd skin rashes, very dry skin, sinus and throat inflammation (chronic), floaters in eyes, etc. etc.  All have tested NEGATIVE for HCV....BUT????
If there is specific organ infection...it is easy to jump to the next conclusion!

What are your thoughts?

Doubledose
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Avatar universal
Interesting comments.  I also had the thirty or so years of 'not normal' bowel movements, soft, loose, wierd...

Also had the small red pinpoint dots on legs and arms which do have a medical name (purpura? I'm not sure)

Also had the soft, always tearing, fingernails and toenails.

Since mid-tx, and ever since finishing tx, all the above have changed for the better.  Normal bowels (amazingly) , hard nails, skin very elastic and with rosy color, etc.  The arthritic pains are slowly fading (which I suffered from for decades) and no headaches!

I assume all these symptome WERE caused by HCV, and it's effect on our immune system.  MAYBE they are resolved.  I sure hope so.

As far as the other organ infection that I have speculated about, I believe that it WOULD indeed be HCV, but in isolated organ systems, and at such a low level that it cannot break into our circulatory system.  I am sure I remember several top hepatologists about five years ago saying that after SVR they still found HCV in the spleen and other organs, but that it should cause no long term problems after SVR.  I thought that was odd then, and in recent years, none of the docs address that issue very openly, so I am not sure what has changed.  Maybe they are all now 'aboard' on the SVR = CURE train, but now other researchers are casting doubt on the idea of total/absolute clearance from all organs.

I do not really have any idea how this 'compartmentalized' infection might work, without reinfecting the person who is now SVR, but I think TnHepGuy ventured some very intriguing thoughts above within this thread.

I see the 'sjogrens-syndrome' type symptoms in myself and family, and several past partners, and I am pushed into thinking there is some common connection.  I have to ask the question:  Why would HCV NOT tend to infect or migrate into salivary tissues, eyes, sexual organs, gastric system , etc. especially when they (researchers) seem to be recovering live virus from those same fluids/tissues (in a wide array of research studies).

If the virus DOES move into those fluids/tissues then we have a much bigger problem out there than anyone realizes.

When they test for sexual transmission, they are testing to see if the serum has become HCV+, NOT whether the sexual tissues/fluids are infected with replicating HCV.  That would call for PCR tests of the specific fluids!

I don't have answers yet, just lots of questions, and observations!

Glad our worst symptoms are no longer hanging around.  That in itself is a major victory.

DoubleDose
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Avatar universal
nonsense=tallblonde
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God it's great to here from all of you. I am off tx about and 4 wks and feeling better. I will test on Monday and we will see what we see. I missed my appointment on Thurs, I have been so darn busy with business and going to court for my grandson.

Anyway God Bless all of you and have a great Holiday what ever you believe or don't belive.


TnHepGuy, chevygal55, Willing, Mikesimon, giddyup, layla tallblonde, doubledose, jonihs, honey15637 and all the rest of you I missed!


Your freind

Bob L


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Avatar universal
Here is my $24 Million Dollar Question for the week:

IF HCV turns out to be a virus that not only infects serum and liver cells, but also possibly brain, lymphatic, maybe even salivary, mucosal, (there have been recent articles by the  Gastro. Asso. that HCV is found in gastric mucosa as well!), sexual tissues, etc then:

1:  What would keep it from replicating in the organs of casual contacts, partners, close family members from things like kissing, sexual contact, etc??  That is, not infecting the blood per se, but setting up a low level, sub-clinical infection in various tissues/ organ systems of our close contacts.  This might be characterized in the same way that SVR's now seem to carry replicating virus in other compartments, BUT NOT in the blood or liver.  That creates an entire new paradigm for the virus!  Do we know for sure that things like CFS, Fibromyalgia, vague autoimmune disease, might not stem from something like HCV infecting perpheral organs, causing autoimmune reactions...arthritis, fatigue, tinnitus, brain fog, etc.  

2:  IF infection can potentially transmit into peripheral organs in other people, would they necessarily have an HCV pos. response to standard serum HCV antibody tests???  Maybe there are many people infected, in non serum/liver organs, who test negative on blood testing!  
(Why do the HCV antibodies NOT go away in SVR's???)  Is the body still detecting HCV??

3:  ARE we yet totally sure that HCV is purely and only a blood transmitted virus????  Recent research is starting to shake my confidence.  Read what Oral Surgeons say about finding HCV in salivary cells, etc.  Why Couldn't it transmit in those tissues?  Or sexual mucosa???? Or mucous membranes..eyes..etc?
THESE are still unanswered questions.  The virologists need to really go to work on these issues. We need ANSWERS, AND treatments.

Food for thought and discussion.  Regards to all of our members.

DoubleDose
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Avatar universal
I just want to ditto what everyone else has said welcoming you both back. You were greatly missed and in my prayers often. Your research and knowledge helped enormously while I was going through tx. and the long months I had to wait to start. God bless you both.   Joni
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Avatar universal
thanks for the kind word. I'm a bit conflicted about the benefits of pursuing hcv research. On one hand it's endlessly fascinating to learn more about such an intimate enemy. On the other other hand it really doesn't help get on with living the rest of one's life. After discovering that, by and large, contemporary medicine understands little and can do less, you're back to attitude and adaptation, regardless of how the ifn/riba lottery treated you. And these are much harder topics to talk about (at least for me) ...so back to Marek and his bad news. It's hard for me to see this as anything but evidence that in most people the virus replicates, in the liver and elsewhere, long after SVR. Negative strand RNA is a short-lived intermediate created during replication and thus presumably harder to detect than plus strand RNA properly ensconced in its protein coat.  
With RNAases constantly chewing up and recycling whatever they run into, the detected RNA would have to be of recent vintage. Purists who want assurance that they've eliminated every last virion probably need to wait until they stop making hcv antibodies and/or show no RNA after taking immunosuppressants. For most people however, "cured" means a working liver and that's not inconsisted with an immune response that keeps viral replication at a low-level (for years and years as confirmed by many studies). Since damage to our liver is not done directly by the virus but by the immune response to its presence, even low-level warfare is not great news, but it's probably good enough to get through one lifetime. Since we're just starting to quantify the impact of infection outside the liver during full-blown chronic infection it seems that any discussion about the impact of residual, low-level, post-SVR infection outside the liver will have to be guesswork for a long time yet. Still, it means that even SVRs may have a reason to be interested in the new meds that directly target the HCV replication cycle.
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Avatar universal
When I found this site a year ago, I began cutting and pasting and printing virtually everything posted by Willing, TnHepGuy and Doubledose. I actually have a file folder full of their stuff.  My own knowledge base was, in large part, developed by learning from them.

Anyone out there who has been recently diagnosed with HCV should pay close attention to their postings (in case you haven't figured that out already).  While this board, unfortunately, can often be filled with nonsense, you can always count on these guys to come through with useful information.

My hat is off to them.

Susan
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Avatar universal
Boy, can I ever relate to that.  My GI tells me to "quit obsessing" about the disease" and "quit reading so much."  He acts irritated if I ask any questions.  The answers he does throw out as crumbs to appease me, are often ridiculous....."I won't be surprise if you clear the virus, but I also won't be surprised if you don't." (Wow!  That sure covers all the bases, doesn't it?).  

It's absolutely maddening and insulting to have to try so hard to tap into their knowledge base.  Wait a minute...maybe their knowledge base isn't as formidable as we think.

Susan
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Avatar universal
<u>mikesimon</u> - congratulations on continuing down the path of SVR. That recent study (though small and limited) showing 100% correlation between 3-month and 6-month PCR/SVR results - if fully born out - is good news for anyone who cares not to wait so long. I've decided to go with a 3-month'er myself. But since my LFT's were elevated prior to tx, I can keep any eye on them and hopefully gain some knowedge via those results prior to the 3-month date.

<u>chevygal55</u> - wonderful news to hear of your SVR. Congratulations and hopefully you can take some solice from that 3-month study (mentioned above) as you go into your 6-month'er.

<u>doubledose</u> - good to see you, as well. This virus truly is a riddle wrapped in a mystery inside an enigma.

<u>honey15637</u> - thank you for the welcome. How are you and hubby holding up here near the end? I'm still hanging on by a thread or thereabouts. I finish all my meds on January 8th.

<u>layla</u> - very good to see you again, too. I hope things are going well for you and your family - especially as you head into the holidays. I'm doing as good as these lousy meds will let me be - and counting the days from here. My guitar playing has been suffering as of late - which of course means that my wife's ears haven't ... ahahahaha. Glad to hear that you're decided to go forward with lessons. You'll be playing like James Taylor in no time flat.


TnHepGuy
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Avatar universal
Great to see you here! How are you doing? Are your sx in control now?  Whats up? I am starting formal guitar lessons in January, are you playing?
What a nice thing to have both you and Willing on the board. I love reading this stuff. I feel fairly knowleageable about HCV and much of it came from info on this board. Glad your back. LL
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<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15554429">Central nervous system involvement in hepatitis C virus infection</a>

<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15548803">Is screening for interferon retinopathy in hepatitis C justified?</a>

<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15498589">Virus evolution within patients increases pathogenicity</a>

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Avatar universal
Thanks for the links above.  The central nervous system issue is one that deserves much continued study!  If the brain and nervous system are indeed becoming infected with the virus, then we need to know whether that infection subsides upon SVR, or if there is a separate, and sustainable infection within brain/nerve tissues that might be the cause of lingering or ongoing symptoms after the 'apparent' SVR.  Maybe there are mutant strains that favor blood/liver, versus nerve/brain tissues, or lymphocytes for that matter.

I do not say this to be an alarmist, but to try to stimulate interest in finding out much more about how this virus works, and why we have this well defined range of multi-organ symptoms, before tx, after tx and for many people well after SVR as well.

I am thinking that, in the case that we are still experiencing disease activity, of a different sort than when our blood and liver was a source of infection, then we will eventually need treatments that will go further, and address the other 'reservoirs' or systems containing either the virus, or some mutated version, or a pathology related to the virus.

I am aiming toward TOTAL cure, somewhere down the road, (MAYBE we ARE already there now, but I have many doubts, in light of all this emerging research), and ideally, with new drugs, we will be able to eradicate the virus totally and permanently, wherever it may exist, and also treat the consequences of having had the virus for years (fibrosis, autoimmunity, brain fog, depression, etc.)

Science is probably lagging behind as far as answering this line of questioning. I waited 30 years to get my SVR, and I am willing to wait a few more to do whatever is necessary to ensure absolute success.  Maybe we won't have to do anything else, but I am keeping an open mind, and watching the new research closely.  No sense in pretending, IF there is another aspect of the disease that we may need to address.

DoubleDose
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Thanks Mike. Hi Willing!
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Welcome back both of you! You both have been greatly missed at the forum!  TnHep,,,How are you feeling lately on the meds and don't you finish up soon?  Best Wishes to you...
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Some thoughts after reviewing the abstract are:

- as far as this study calling into question long-term SVR, I just don't see it in there. "<i>Viral sequences were also detected in livers from 3 patients (180 to 466 genomic eq/?g RNA), but negative strand was not found.</i>" This information coincides with the study (I don't have it handy now) from about five months ago which showed partial viral persistance within the liver in some long-term SVR's, but no replication taking place. Given that the liver truly is the place where the virus both breeds and dies, any relapse after long-term SVR would seem to have to involve negative strand RNA replication within the liver - from which it could then 'explode' into the rest of the body. And it doesn't seem unusual at all to find viral 'remnants' and 'crumbs' left over within the body after infection. For example, this happens after someone has the flu virus. Also, the earlier study looked at both chemically cleared SVR's (i.e. - interferon-induced) as well as spontaniously cleared SVR's. And each showed similar traits in terms of viral remnants and negative strand RNA. And most telling of all to me is that in neither of these long-term groups (interferon group - 10+ years post SVR; spontaneous group - quite possibly even longer clearance) is there any hard, clear data showing relapse years down the road. They remain virus-free and in general show the improvements in liver histology, etc. - that are associated with long-term SVR.

- possibly disturbing in this study, though, is that it does show "<i>HCV RNA negative strand was detected in 6 (21%) of 29 HCV RNA positive cultures</i>" in lymphocyte and macrophage samples. This may point to very low-level, non-replicable persistance being held in check by the body's immune system (as refered to by 'willing'). Which leaves open the question of what could possibly happen if one's immune system were to become compromised at some stage in time. Would the negative strand RNA then be able to 'overwhelm' the 'balance' that had been in place, thereby making it's way into the liver to begin the accelerated 'breeding' process?

- also potentially disturbing is what 'doubledose' has eluded to: what could the possible long-term effects be from having low-level persistance occur within certain areas of the body, irrespective of if there is any relapse or not? Could this possibly explain things like auto-immune and similar affects? Does the immune system therefore always remain 'suboptimal' as a result, since it has this constant battle to fight? Is this negative strand persistance in other areas/tissues of the body, and causing long-term sx's as a result? Also, it would seem logical to assume that if this type of persistance does cause problems in SVR's, it would also cause the same type of concerns in anyone actively infected with HCV, too.


TnHepGuy
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