Article on Occult/Persistence and Other Posts

Here's a good, comprehensive article by one of the leads (Pham) on research into occult Hep C:

<a href="http://www.findarticles.com/p/articles/mi_m3230/is_2_38/ai_n16084704">Occult hepatits C virus persistence: identification and characteristics</a>


(from the article):

"<i>Although HCV is considered to be primarily hepatotropic, accumulated evidence clearly indicates that the virus also invades and replicates in the immune system. In fact, the presence of both HCV RNA positive and negative strands has been demonstrated in lymphoid cells in both in vivo and in vitro settings. For example, T cells, B cells, monocytes, and dendritic cells from patients with chronic hepatitis C have all been shown to carry HCV genomes. (2), (10-12) Most recently, by applying assays of superior sensitivity mentioned above, replication of HCV has been seen to persist in lymphoid cells for years after spontaneous recovery or a sustained virological response to IFN-alpha/Ribavirin therapy. (1-3) In addition, low levels of HCV RNA in lymphoid cells have been detected in a significant proportion of patients with persistently elevated liver enzyme levels of unknown etiology. (13), (14) Along the same line, susceptibility of T and B cell lines as well as primary human T cells and macrophages to HCV infection have also been documented. (15-18)</i>"

[TnHepGuy_]

"<i>Occult HCV infection

In our studies, using the highly sensitive RT-PCR/NAH assays, conclusive evidence was obtained for the presence of replicating HCV in persons who apparently completely recovered from hepatitis C and whose sera were repeatedly negative for HCV RNA by standard assays. We found that more than 80% of these individuals were serum HCV RNA positive at levels usually not exceeding 1[0.sup.2] vge/mL and that 30% to 40% of them also carried HCV RNA in circulating lymphoid cells at levels between 10 and 1[0.sup.4] vge per 1[0.sup.7] cells (see Figure 1). (1), (19)

However, when the cells, including those apparently negative for HCV RNA, were ex vivo treated with mitogens known to activate different immune cell subsets, e.g., phytohemagglutinin (PHA) to stimulate T cells, pokeweed mitogen (PWM) to induce B and T cells, and lipopolysaccharide (LPS) to activate monocytes and B cells, HCV RNA was detected in all of the individuals. (1), (2), (19) Interestingly, in the majority of the cases, synergistic stimulation of T and B cells and monocytes with mitogen cocktails led to a more pronounced upregulation of HCV RNA expression than did single mitogen treatments, suggesting that all three cell subsets are reservoirs of the virus (see Figure 2). This propensity was also found when the same cell subsets purified from hepatitis C patients were analyzed. (2), (19) Overall, the ex vivo synergistic mitogen stimulation of peripheral lymphoid cells allows for a more precise detection of silent HCV infection than by testing either sera or naive (untreated) lymphoid cell samples alone. Our original identification of commonly occurring occult HCV infection has been corroborated by recent data from several other laboratories. (3), (4), (6) This collective evidence challenges the previous notion that resolution of hepatitis C reflects complete virus eradication. Further, the invariable detection of replicating HCV genomes in lymphoid cells from individuals with either occult or symptomatic infection attests to the existence of an extrahepatic compartment for HCV replication.

In addition to consistent identification of HCV RNA in ex vivo stimulated peripheral lymphoid cells, HCV RNA has also been detected in liver tissue of asymptomatic individuals with a sustained response to antiviral treatment. (3), (5) Although these patients generally exhibit histologically apparent improvement after IFN-alpha/Ribavirin therapy, including partial regression of fibrosis, liver biopsies from many of them show evidence of persistent minimal inflammation or even of active chronic hepatitis. (3), (5)

Implications of occult HCV infection

Although investigations on clinical relevance of occult HCV infection have just begun, the data available at this point could help explain sustained HCV-specific T-cell responses observed in individuals decades after recovery from hepatitis C. (8), (20) In this regard, the presence of low amounts of the replicating virus could provide continuous antigenic stimuli beneficial to immunocompetent individuals in maintaining an effective antiviral immune response and keeping the occult infection under control. On the other hand, virus persisting at very low levels may provide a means for reactivation of infection when the host's immune system becomes compromised due to a disease or therapy. Indeed, reactivation of HCV infection has been documented in patients receiving immunosuppressive treatment. (21), (22) Along the same line, HCV RNA was also detected in sera of anti-HCV positive patients weeks after acquiring HCV-negative kidney (23) or bone marrow (24) transplants and immunosuppressive therapy. With respect to commonly observed HCV reinfection of liver allografts in patients with end-stage diseases caused by chronic hepatitis C, migration of lymphoid cells, including those carrying not readily detectable quantities of replicating virus, may constitute a main mechanism by which the transplanted liver becomes infected.

In summary, occult HCV infection is a common, if not an invariable, consequence of resolution of hepatitis C when measured by highly sensitive assays established recently in some research laboratories. The availability of assays detecting HCV RNA with a comparable sensitivity in clinical laboratories would improve the precision with which HCV is detectable among patients and in the general population. Furthermore, the persistence of traces of replicating HCV in lymphoid cells, from which viral infection may potentially rebound under favorable conditions, suggests that future treatments aimed at HCV elimination should take into consideration that both the liver and the lymphatic system are the sites of virus propagation.</i>"



TnHepGuy

[mikesimon]

Thanks for the article. Mike

[fishdoc]

When I first started reading the forum, a couple of months prior to tx, it seems to me most agreed the beginning of tx was the "worst" time.  Others seem to feel that last month was by far the worst... I am starting into month 4, and I am dragging NOW.  Would anyone mind a thread where those that have passed before us rate treatment? Just to give us more to worry about...
Mine so far:
Month 1  no problems
Month 2  some fatigue
Month 3  fatigue increasing
Month 4  fatigue is getting to me, some nausea
Month 5
Month 6
Month 7
Month 8
Month 9
Month 10
Month 11

[Chriskid]

It

[Dale_Ray]

Month One - So screwed up thought I would just die
Month Two - Not much better but couldn't breath when I walked
Month three - Much improved adjusted to low energy levels
Month four - Fatigue and weight loss problems
Month five - not so bad just tired and feverish
Month six - I lose myself in the middle of thoughts and fatigue
Month seven- Hopeful (not there yet)

I wish I had kept the diary they gave me at doctors office. There have been so many ups and downs so far. I hope you feel better soon. Dale

[FlGuy]

This topic, different instance, was mentioned here a few weeks ago and got my attention. Since then, I had an appt. with a gastro who is going to do a colonoscopy and an endoscopy this month. I asked him then if the use of of unclean instruments and cleaning protocols were an issue in the clinic where he he scope. He had heard of such instances elsewhere and tried to assure me that all the celaning (including equipment enzyme spraying) is religiously adhered to. I guess it's a matter of trust that people and facilities follow the rules.  Just in case, I asked him to make sure that they do the endoscope (top down) before the colonoscopy (bottom up).  Don't want to have embarrassing bad breath from it.

[MrsOckert]

As has been stated before it is soooo different for everyone.

My first couple weeks were livable.  Not pleasant, but if that was as bad as it got I could do it.

Week 6-12 I thought I would die.  Literally every day thought I was dying.  Heart palpitations, couldn't walk, breathe or anything.  got the thyroid regulated and felt better.

Had a few good weeks.  Weeks 23 - 30 (current) I've been sick every week.  Weekends are spent with fevers and body aches and pains that don't leave till Sun eve.  The last couple weeks the metal taste in chest and mouth along with GERD, has been particularly bad.

Fatigue and weakness lasting thru the week has been particularly bad.  

Panic attacks stopped a couple weeks ago.  Didn't lose any weight the first 24 weeks - lost 35 lbs since then.  

For me the sx's have been worse the second half of tx.  I hope they clear up soon.  I'd like to have one week of no sx's.

[DoubleDose]

The article cited sort of sounds like the same thing that I have been hypothesizing , albeit my rationale is less scientific, for several years now.  
I really do believe there is much more than meets the eye regarding how this virus works, and where it 'goes' after successful tx (and before tx, for that matter).

My ongoing emphasis is for the research community to pursue this issue aggressively, to determine what, if any, health consequences this ongoing 'persistent infection' might have.  Issues like ongoing autoimmunity, lymphocyte related diseases, and so on, should be explored thoroughly.  We also need to understand why over 50% of SVR's seem to manifest the same pre-tx symptoms long after they are 'cured' of the virus.(several HCV doctors I have spoken with refer to this statistic).  Maybe it has a major connection to the 'persistent virus' replicating at very low levels in various 'compartments'.

ALSO, we need clear answers on whether or not HCV can truly 'infect' the nervous system tissues, the brain, spinal column, gastric tissues, etc.  Studies are always in conflict over these questions, and about half fall on each side of the fence.  Science should be doing better than this!  Research studies need to be designed to determine positively, whether this happens, and how many organs it might affect.

My ongoing concern and suspiscion, is that this virus is really NOT just a 'blood/liver' virus.  It may like many different tissues.  The article above seems to agree.

DoubleDose

[jmjm530]

Fl,

Sure like your doctor and nurse always wash their hands before examining you and after touching a surface that might be contaminated. Like the nurse always follows correct protocol for taking your blood pressure, etc, etc. If the lax attitude I notice in hospitals and doctor's offices carries over into instrument sterilization there's bound to be trouble. A news article several months ago talked about how easily infections are spread in a hospital, and how you can walk in relatively healthy and end up sick.

Fish,

Week 1 -- Sucked
Week 2 -- Sucked
Week 3 -- Sucked Big Time
Week 4 -- Sucked Big Time
etc, etc,

[FlGuy]

I've always assumed that the greatest danger in getting sick is at hospitals. Lots of yukky stuff happens there, and all those sick people too.
The scopes on 5/22 are the last pieces before getting more opinions.  Every other test is done and no older than 1-2 months, with the excpetion of the year-old bx. The bx slides are being held for me at the hosp. pathologist.  First stop is a local hepatologist and then a univ. liver clinic - both by the end of June.  Best guess is more tx start in Aug or Sept, want to get some value from the summer (kids off, family vacation)then I'm guessing 36 - 48 weeks.
I did not (pre-tx, 12 week, 24 week or 6 month post) have sensitive pcrs. Figured, maybe unwisely, that if detected (espicially post tx) would be greater than 600 anyway. At least that turned out to be true.   It's a topic for re-tx that I'll study more, lots of good info being shared on the topic here.  Will, however, do a 4-week next time.  I guess I underestimated 3a - lulled by high success rates.

[jmjm530]

Hey, what happened to your "no clinical signifcance found yet" disclaimer. LOL.

re: "We also need to understand why over 50% of SVR's seem to manifest the same pre-tx symptoms long after they are 'cured' of the virus"

Very difficult to isolate what pre-tx symptons were caused by Hep C and what aren't, given the fact that many report no symptons. As to symptons after SVR -- many may be caused by the treatment drugs themselves as you have posted about before.

Just want to emphasize again that these under the radar viruses appear to have no statistical threat regarding relapse, as SVR is durable to around 99% and close to 100% after being non-detectible for one year. And as of now, no clinical significance has been attibuted to any of these under the radar viruses.

But as you say, hopefully the research will go on, and hopefully it will benefit all of us in a meaningful way. Until then, SVR is our cure in the true sense of the word both because of its durability and the fact that it's linked to stoppage and even regression of liver damage. Maybe one day there will be a more complete cure, maybe not.

-- Jim

[LvdByGod]

first year sucked!
second year sucked!
this year...well you get it!



actually for me my hardest time was "mid" treatment... the ringing of the ears freaked me out and the anxiety. the eye and gum problems and the feeling sick and tired and being worn out, the sleeplessness and sleep deprivation, just finally got to me... the social anxiety and not being with it mentally...the brain fog!!! toward the end months i definately had adjusted to the sx... though they still sucked, they did get easier to deal with!!!  

for me it wasn't really the initial flu symptoms those went away...nor was it the end time panic and fear of getting off to find out the results, although that was really dificult. it was the grind of it all, in the middle when there seemed no end in sight... this is was the hardest for me... thank goodness for the zanax, ambien, and ad, they really helped me through that time...

it does end though, and it is doable...and i am definately starting to feel some relief now that i'm done!!!

but, in a few weeks i have my first post tx pcr!!! yikes!!!

sandi

[landfill]

Infections from unsterile resued instruments was in the news a few months ago.  I think there's a scandal there waiting for somebody to blow the lid off.

The way I get it, instruments designed for a single use are being "reprocessed" and reused.  The hospital buys them from a reprocesser and uses them, taking on faith that they're clean.  Some of the reprocessors have dubious qualifications.  Since each instrument is different, there aren't standards for how to do it.  Some of them are destroyed by heat.  Since they were designed for a single use, sterilization wasn't a factor in their design.

To top it off, hospitals have a single price for an instrument.  They don't distinguish between new ones and reprocessed ones.  So some suspect they charge new prices for tools that cost them a fraction of the new price.

The next time somebody wants to stick a tool in me I'm going to insist that it's new.  Does anybody know if the health insurance industry has weighed in on this?  Will they pay for a new tool if a used one is available for less?

[NYgirl]

HEre are my little numbers if they will help you i'll put it down

Month 1 Lethargic / RibaRash / Losing Weight
Month 2 Anemic / Totally DEVASTATED / RibaRash / Losing Weight - Hair
Month 3 Recovering from anemia... extremely lethargic /RibaRash / Losing Weight and Hair
Month 4 Lethargic / Found Gold Bond Rash going away / Losing LOTS of hair
Month 5 Lethargic Losing LOTS of hair
Month 6 Lethargic / Thyroid Diagnosis / Hair and Weight Leveling
Month 7 Getting a bit more energy (maybe the thyroid med?) Weight level, hair not falling out as bad
Month 8 Here Now doing OK no major problems
Month 9
Month 10
Month 11
Month 12

I definitely had many more problems in the first few months. Hopefully this will continue on like it is or even better - I never want to go to anemia land again.

It seems like for ME month 7 was the real turning point.  I don't know why but...

I hope that helps!

[sailinlady]

I have to agree with Jim on the "sx experiences".  Yesterday was by far one of my worst days for riba rage.  I just wanted to beat the **** out of everyone, my husband, my best friend, my step daughter, my mother in law and anyone else I came in contact with.  Fortunately, I'm really not that kind of person and even if I were, I would not be strong enough!  LOL. So, I walked around the house cussing everyone out under my breath.  I'm thinkin' they all knew well enough to stay away and give me my space.

Shot 44 tomorrow.

[TnHepGuy_]

This article - along with the <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16537674&query_hl=1&itool=pubmed_DocSum">Comar et al</a> study and the <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16628675&query_hl=1&itool=pubmed_docsum">Giannini te al</a> study posted by 'willing' - are a set of research beginning to show that occult can/does have it's own set of potential implications:


- Giannini shows a direct cause/effect relationship between occult and cryo.

- Comar points to a relationship between occult and HCC.

- the Pham paper above mentions that the Radkowski et al and Carreno et al papers point to a relationship between occult and continued histology post SVR: "<i>Although these patients generally exhibit histologically apparent improvement after IFN-alpha/Ribavirin therapy, including partial regression of fibrosis, liver biopsies from many of them show evidence of persistent minimal inflammation or even of active chronic hepatitis.</i>"



The practical message to HCV patients is: just because you've cleared the virus (SVR or spontaneous) doesn't necessarily mean that your viral story may be over. It would be prudent for patients and their caregivers to keep a close eye on things via appropriate periodic testing (eg. - CBC, Liver Panel, AFP, Ultrasound, possibly bx for those with more advanced histology prior to viral clearance, CAT scan, cryo, etc). And to find a doc/group who keeps current with ongoing developments in HCV research and developments - not to mention keeping current yourself. Any doctor who thinks "SVR=cure" and "out-the-door-you-go" is now in the stone age.



TnHepGuy

[jmjm530]

I would imagine your odds of contracting something from a colonscophy are FAR outweighed by your increased chance of colon cancer if you don't have the procedure.

I've had two of them in the last ten years and with modern technique and medications they are entirely painless, with zero discomfort.

The sedation used works fast and wears off mostly within a half hour post procedure. You're in the office and out the door within a couple of hours.

As many will testify, the worst part of the colonoscophy is the prep 24 hours before where you have to drink some solutions to clean out your bowels. But even that has changed radically in the last ten years and now it's really no big deal.

Neither of the two procedures you mention will be able to snip a polpy out on the spot and then biopsy it. I've had a few removed during the procedure and later biopsied. Fortuntly they were benign.

Now cystoscophy is another animal and is a truly barbaric procedure at least for men.

[sunspot]

Doc
Month Ten. Hanging on the edge of a tall cliff with broken torn fingernails and bleeding fingers.
Month Twelve. Off tx 30 days. Ahhhhhhhhhhhh

FlGuy.
See you in the middle.

[jmjm530]

Thanks! I'll report back if I can lasso his attention long enough for a meaningful response.

[GoofyDad]

You say: I felt zero pain and discomfort both times

Prolly 'cause you're busy making goo-goo eyes at the cutie from the vitamin store. Is she there for the thrill, running the scope, or maybe she's the ring from the box, like the dentists gave out when you were a kid?

[FlGuy]

I followed the prep directions to the letter too, including the timing, fluid intake, meds - all of it. He wrote, I followed. Good thing there wasn't a fan to hit.

[DoubleDose]

Thanks to both of you for your further interpretation of the 'viral persistence' studies, and your explanations of the actual evidence that is amassing regarding the 'clinical significance' of this phenomenon.  The fact that a variety of potentially lethal illnesses (HCC, Lymphoma, etc.) are now being linked to post-SVR viral infection / or compartmentalized low-level infection, is enough to cause all the HCV doctors to drop the 'clinically insignificant' disclaimers when this subject comes up, and to start 'digging in' to the real challenge:  identifying how this post-SVR 'infection' really works, what it is capable of doing to us, and how it might also be addressed by therapies, in the future.

If they were able to develop successful therapies for the blood/ liver infection, you would think that pushing the science to discover just what might fully eradicate this virus, would be doable, even if difficult.

Regards to all.

DoubleDose

[landfill]

The controversy is about disposable items which aren't disposed of.  A colonoscope with the headlights, webcam, windshield washer, snipper, etc. is made to be sterilized and hopefully they do it right.  The disposables aren't made to be reused and maybe can't be cleaned reliably.

[Boomer314]

I just found out that I am going to have to go on interferon for type 1A hepatitis C.  My doctor started me on an antidepressant already.  Will this help with the panic attacks?  Can't they do anything for the fatigue?  I can't really miss a lot of days at work and I don't want to tell people at work what I am on.  Will it be possible to act like nothing is going on?

[cuteus]

tnguy/willing, are you guys using persistent HCV and occult interchangeably? as I read those abstracts, they seem to be of persons that did not treat for HCV but tested positive in non serum samples. In some of the other abstracts I read on SVR with pos HCV in the liver and PBMC but not in sera, it did not seem that it was found in 100% of patients.
If I was to search for studies that found no traces of HCV in PBMC and liver tissue, I probably would come up with enough to match the ones presented, or maybe not. It is possible that researchers in hopes of getting published find that controversial subjects like persistence might get more attention than those stating that all is well? I don't think all studies get a predominant spot in the news.
excerpts of discussion of non persistance include the one from natap.org
"A study of 12 patients who achieved SVR after 24 weeks of interferon-alpha2b / ribavirin treatment was conducted by researchers at the Huddinge Hospital in Sweden. The study found that 11 of the 12 patients remained HCV RNA negative 2 years after the termination of treatment.  
In addition, these researchers found that in 9 of the 12 patients biopsied at the 2-year follow-up, liver inflammation had disappeared completely and fibrosis had improved.

A study conducted by researchers at the Karolinska Institutet in Stockholm, Sweden examined a group of 26 patients who had achieved SVR after interferon therapy for periods ranging from 3.5 to 8.8 years.

Of the group of 26 patients, 22 patients had normal serum ALT levels, 24 patients (92 percent) were HCV RNA negative in serum, and liver biopsies performed in 23 patients 2.1 to 8.7 years after end of treatment showed no or minimal liver inflammation. Mild and probably irreversible fibrosis was seen in a few patients."

So, it is possible that the biopsies did not include a PCR for HCV, but the improved fibrosis could indicate eradication of the offender.
It does seem as if the occult theory has a lot of backing, but I still don't buy the persistance theory, not in all SVRs.
I don't have time to look for the bookmarks on zero hcv finding in SVRs in the hepatic and PBMC, but I am sure you guys have seen them.
Can anyone say absolutely that all SVRs harbor persistent HCV after tx? Especially when some tested show negative results in both serum and liver/PBMC?

I do hope someone who is presently researching that 'all is well' gets published.


I still think a hepatitis cure is achieved in some of people treated for HCV, and so did my hepatologist at his last talk, not too long ago. Sorry to hear he might be stone age, since he heads the dept.
HCV seems a very addictive subject matter, even for SVRs.

[jmjm530]

Regarding, the revision to the disclaimer :) -- Do me a favor if you get a chance. Please pick the one study you feel best makes your point that there's meaningful clinical significance to occult/persistent virus. If I get a chance I'll try and run it by my doc whoese opinion I respect. I doubt if I will have time to run two papers by him. As I've stated before, the last conversation I had with him on persistent/occult virus -- while he acknowledged their presence, he seemed to question their clinical significance as well as their replicating status.

[DoubleDose]

I do not think that remaining SVR for 'x' years after tx, or maintaining HCV liver status on biopsy are the issues here.  The research is suggesting a 'low-level' viral replicant found in liver, lymphocytes, PBMC, etc which does not show up on standard HCV PCR tests of blood or on standard liver biopsy.  The question that is important is this:  what does this persistent infection do from a health standpoint? and, is it really there?

The studies that I have read regarding 'persistent HCV' after SVR, (not Occult HCV, which is different), have indicated finding HCV RNA in the PBMC's many years after SVR, and finding it in the great majority of those studied.  Now, I agree, these reports may be controversial, and may also be contradictory to some other research reports...but that is just my point!  The research community needs to unequivocally determine whether this is indeed a fact, or not....and if it is...they need to really figure out what the long term implications involve.

Just a few years back, the medical community looked at HCV as a sort of benign infection that could be 'lived with' successfully.
That picture has changed dramatically as liver related mortality continues to tick upward, and as other related illnesses have become linked to HCV.  Now we are seeing another similar approach to the possible 'persistent virus' issue.  'we have not seen any clinical significance'....etc.  Well, sure....they have not really looked closely yet.....nor have we studied the longer term consequences of this potential lingering infection on SVR's after 10, 15, 20 years or more.

I just want good science....not 'wishful thinking' or 'happy talk'.  Obviously, if there is more to the picture, the drug companies are not going to push for much in the way of communicating this information, or asking the harder questions about the consequences of 'persistence' if it is a reality.
We do need highly objective scientists and impartial medical experts pursuing the answers.

DoubleDose

[DoubleDose]

In regard to your comment to Willing, I will echo what I just said to cuteus:  I do not think the doctors, even the really best HCV doctors in the world, have the answers to your question yet.  You can run these studies by any of the doctors out there, and you will probably get the same, 'stock' answer that you anticipate:  'we have not seen any clinical significance'.  That's right, because they have not yet really studied the issue yet....they are only beginning to acknowledge the existence of 'persistent' virus, and I personally do not need to be 'reassured' by hearing an answer that 'feels good' but has no real basis in research yet.  
Sure, we understand, the virus is no longer active in the blood, or liver.....liver histopathology is changing for the better in SVR's....life expectancy is probably much improved...etc.  

But all of that begs the real question:  What about this 'persistent' stuff?  What might IT do to us long term?  And, does it have any effect on our immune systems, our chances for HCC, our susceptability to other diseases....Lymphoma, Lupus, etc? (some of the recent research is starting to point to 'yes' as a possibility)

I do not believe that your doctor, or any other doctor out there, has real, valid, supportable answers to these questions yet.  Only suppositions, and opinion.  

DoubleDose

[jmjm530]

I think we're more in agreement than you may think.

What I think you're saying is that no clinical significance has been proven one way or another and therefore more study is needed. I'm saying these claims have no clinical significance and therefore not overreact or scare ourselves (or other people)and yes, more research would be appreciated.

But I *think* Willing is saying something different from either of us. In Willing's words " (Jim) perhaps you should consider qualifying that "no clinical significance has been attibuted" disclaimer in light of those recent papers."

That's why I offered to show a paper to my doc to see what he has to say regarding the clinical signifiance of the "recent papers" Willing alluded to.

Quite honestly, I don't have the medical or experiential background to put all these papers (many conflicting) in the kind of context necessary to make any definitive statements.

-- Jim

[jmjm530]

I'm surprised to hear you had a bad reaction to the procedure. Possibly you should consider switching to another doctor who uses some of the more modern sedation techniques.

I felt zero pain and discomfort both times, and even watched the procedure on a tv monitor until I dozed off. I've heard similar stories from many others as well about how painless the procedure was. I mean on a scale of one to ten where ten is having a cavity filled, this rates a zero. I traveled out of my way to NYC to have mine done, just because of the reputation of a doctor there. Colonscophy's and endocophy are pretty much all he does besides teaching and lecturing on the subject. His name is Dr. Jerome Waye and practices in New York City.

He's not only one of the best in the drilling business, but one of the most thoughtful and considerate physicians I've ever visited and his office is an example of modern technology and efficiency. Keep in mind you may have to book an appointment six months or more in advance.

[Dale_Ray]

I believe that the test facilities probably have operating standards concerning instrument cleanliness and processes. I would imagine prior to each colonostopy (spelling ?) they pull a brain surgeon out of surgery to clean the big silver snake. Let's face it the whole thing is about the individual. A trainee gets the cleaning duties in these matters and some are good and others...........well they should follow another career path. Have a little faith is about all you can do. Good luck on your procedures and hope all is well. Dale

[FlGuy]

The procedure wasn't bad.  I woke up in the same position I was put out in and was unaware of anthing going on around me. I'm sure they threw me around like a side of beef in a food locker. My main issue is the need to check all modesty at the door.  You would think that after all the procedures (scopes, hernia check, prostate exams, mri etc) that I'd get used to it. It was kind of funny, if not embarrassing, when the first thing the doc said to me upon waking was 'you'll need to do a better job of cleaning yourself out next time'.  Yeah, like I don't deal with a lot of **** from you either, doc.

[mikesimon]

I very seldom laugh out loud at anything I read here, or anywhere for that matter, but you made me laugh. Did the doctor really say that to you when you awakened? These guys kill me - well not quite but close. When I practiced law I had occasion to have a couple of docotrs as clients. They were in divorce actions and they were the most uptight and demanding clients I ever had. I'd make them wait sometimes just because they were such jerks. I can hardly believe the guy said that to you. It is way over the top. Do you have these procedures frequently for him to say that - like you'll be coming in for another one next week? I mean that is a strange thing to say and I'm still laughing about it. Mike

[willing]

tn: good summary, thanks for the post. Here's a <a href="http://www.mlo-online.com/articles/0206/0206clinical_issues.pdf">pdf</a> version that includes the images and cuts down on blinking-induced  headaches.
jim: perhaps you should consider qualifying that "no clinical significance has been attibuted" disclaimer in light of those recent papers.

Arguing against post-SVR persistence is starting to look like arguing against global warming (here's yet another study <a href="http://www.scipub.us/fulltext/ajid/ajid1134-42.pdf"> Falcon, et al. </a> ). None of this lessens the value or durability of that elusive SVR. However, given that even the well-established liver-associated risks of HCV are seen as infrequent/intractable enough for public health to address on a large scale it's hard to imagine post-SVR research getting much attention..

My reading, for obvious reasons,  has shifted towards, the new <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16107835&query_hl=4&itool=pubmed_docsum">structure-based  drugs </a>. This is one well designed, slippery, little critter... regardless of what we throw at it, it manages to mutate just enough to get by. There may be a lesson about staying flexible in there somewhere.

[willing]

I actually got back a report card on how well I had done on that elaborate pre-op prep... and got flunked with  a "poor", though I had followed all their instructions. I guess they get tired of guiding their scope through all that s**t, particularly when they've just come back from lunch.

[FlGuy]

He said it and waited to speak to me until I was awake and my wife was present. Since he's not my primary I see him only for these 'special occassions'.  But when we spoke last week I told him that when he does the endo and colon scopes later this month, do the endo first.  Much like a car mechanic, I don't care if he cusses - just make the darn thing run. I'm just glad he changed his scrubs before I woke up. I may have tie-dyed him.

[willing]

as best I can tell, the following are "true", meaning they are accepted by nearly everyone working in this field :

1. undetectable RNA in serum during tx, regardless of the sensitivity, does not signal the absence of infection

2. undetectable RNA in serum 24 weeks post-tx (SVR) signals either the absence of infection or a tx-induced change in the body's ability to contain residual infection

3. SVR is durable in at least > 95% of patients, probably more

4. the major health impact of chronic HCV infection is fibrosis (->cirrhosis,esld,hcc)

5. HCV is also associated with many non-liver complications, eg cryo

6. attaining SVR significantly improves the outlook of patients with respect to liver impact, extra-hepatic benefeits are not as well proven

the following seems "well established" meaning  that a literature search  in an indexing database (ISI) of all papers that have cited <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15140984&query_hl=7&itool=pubmed_docsum">Pham, et al '04</a> turned up no citations that refuted the finding and at least a half-dozen that corroborated it

7. undetectable RNA in serum post-SVR may not signal complete viral eradication. In particular careful examintion of cells from a variety of tissues shows the presence of both HCV RNA and its replicative intermediate in many but not all patients.

I posted this list of  cites a while back. If this finding were controversial the list would have included papers that challenged it. By itself, the finding doesn't prove that the RNA detected is associated with mature, infection-capable, virus and that even if it is that there is any health impact from the persistent low-level infection. However, a recent small study <a href="http://www3.interscience.wiley.com/cgi-bin/abstract/112595728/ABSTRACT"> Giannini, et al '06</a>  confirmed (7) *and* reported a strong correlation between the presence of post-SVR infection of PBMCs and MC effects :

<em>"We analyzed 9 consecutive HCV-positive patients with MC who showed sustained virological response after treatment. An extensive follow-up showed persistent HCV RNA negativity both in serum and liver samples via very sensitive detection methods (Table 1). In contrast, mitogen-stimulated11 and uncultured PBMCs were HCVRNA–positive in 5 cases (Table 1). Detection of negative-strand HCV RNA via Tthbased reverse-transcriptase polymerase chain reaction confirmed activecell infection in most cases. Interestingly, isolated lymphatic infection was strictly associated with the persistence of both MC-syndrome and t(14;18)-bearing B cell clones (Table 1)." </em>.

That's only one small study, obviously preliminary, but more than speculation.

Jim: I'd pick either the Pham review or the Giannini paper depending on whether you think (7) or its health implications are more interesting.

[FlGuy]

I agree about the risks of not having a colonoscopy.  I have a family history of colon disease and a year ago the doc harvested a couple of polyp beauties.  The feeling for colonoscopy, for me, is beyond dread and hate.  But, I'm committed to annual (no pun intended) reaming. Besides, I would be surprised if those pill-cameras were single use.

[TnHepGuy_]

<u>jmjm530</u>

You may want to print out the pdf file that 'willing' linked to in post #32 above. It is the most up to date summary of all the research on occult so far - and includes plenty of references for further digging, should your doc so desire. It's the one I would bring to mine to: 1.) discuss occult with him and 2.) to see if he is up to speed, has an interest in or is merely dismissive of occult (not a good sign).

I talked about it with my doc about a year ago. At that time he said that occult Hep C had been speculated about then known of for a few years already.

When I asked him about the possible implications he said, "who knows? No firm research yet". When I pressed him about keeping a closer eye out even though I'm SVR, he agreed that I should see him every six months - with a full battery of testing done over the course of each year. When I asked about a theoretical attempt to tx it down the road with some future, unknown drug - he said that docs and insurers would balk at it since "SVR" is the accepted "cure". And he suggested that what needs to be weighed most in that type of tx'ing is the possible physical costs of attempting to wipe out every last viron - since any drug regime will come with some potential consequences.


<u>cuteus</u>

And, as far as any differences in "occult" vs. "post-SVR persistence", other than semantics I really don't see any. In one instance you have a group of patients who are serum cleared spontaneously. In the other they have cleared serum chemically - the end result being that both are now left with the same low-level "bugs". Researches may approach the groups/sub-sets differently for study purposes, but on a practical level both sets of patients are left in the same viral boat.

And, while some studies have shown occult not being present in all post-SVR or spontaneous clearer's, the Pham study above mentions this: "<i>However, when the cells, including those apparently negative for HCV RNA, were ex vivo treated with mitogens known to activate different immune cell subsets, e.g., phytohemagglutinin (PHA) to stimulate T cells, pokeweed mitogen (PWM) to induce B and T cells, and lipopolysaccharide (LPS) to activate monocytes and B cells, HCV RNA was detected in all of the individuals.(1), (2), (19)</i>".


TnHepGuy

[sfbaygirl]

I possibly got this HepC in the hospital.  I had an eblazion of the uterus (out patient) 10 years ago.  I went home and ended up back in the hospital with sepicemia, high fever, joints that hurt so much I could hardly move and red hands and blotchy.  They finally found very elevated liver enzymes and hep C.  Of course,  they say they didn't do it!  The anthesist looked pretty sleezy.  I was sick for a month and didn't have any symptoms for 10 years.

watch out for those instruments!

[jmjm530]

TN said:When I asked him about the possible implications he said, "who knows? No firm research yet". When I pressed him about keeping a closer eye out even though I'm SVR, he agreed that I should see him every six months - with a full battery of testing done over the course of each year. When I asked about a theoretical attempt to tx it down the road with some future, unknown drug - he said that docs and insurers would balk at it since "SVR" is the accepted "cure". And he suggested that what needs to be weighed most in that type of tx'ing is the possible physical costs of attempting to wipe out every last viron - since any drug regime will come with some potential consequences.
----------------------------------------------------
Thanks for the suggested print-out for my doc! Hopefully, there will be time for him to go over.

From what my doctor has  told me so far, I wouldn't be surprised if what he says is almost identical to what your doctor told you. To me, your doc's words sound reasonable and probably more or less "conventional" wisdom among many leading hepatologists. As future treatments, etc, while he voiced some reservations, the implication is that if new evidence warranted treatment, he would of course do so. Again, I would imagine my doc would have the same point of view -- and would jump on any new treatments (even for SVRs) once he was convinced the benefits outweighed the risks.

I'll still try and have the discussion with my doc, but my question to you is -- did your doctor's statement above sound reasonable to you? Because it more or less reflects my thinking as well and we therefore may be more or less on the same page.

All the best.

-- Jim

[jmjm530]

Which was the study that suggested that the occult/persistence replicated? If I read my doc correctly last time, he inferred that the viral remants found were not replicating.