(this first study discusses negative-strand HCV RNA)
<a href="http://www.natap.org/2006/HCV/012506_01.htm">Significance of liver negative-strand HCV RNA quantitation in chronic hepatitis C</a>
(these relate to occult)
<a href="http://www.natap.org/2005/HCV/010305_04.htm">Persistence of hepatitis C virus in patients successfully treated for chronic hepatitis C- 2 Editorials</a>
<a href="http://www.natap.org/2005/HCV/090505_20.htm">Occult HCV- HCV RNA Found in Liver of Patients Negative for Antibody-HCV & Serum HCV RNA</a>
<a href="http://www.natap.org/2005/HCV/090505_10.htm">EDITORIAL COMMENTARY Hepatitis C Virus (HCV) Occult Infection or Occult HCV RNA Detection?</a>
<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15831916&query_hl=1&itool=pubmed_DocSum">Hepatitis C virus replicates in peripheral blood mononuclear cells of patients with occult hepatitis C virus infection</a>
<a href="http://www.medscape.com/medline/abstract/14702147?queryText=occult%20hepatitis%20c">Occult hepatitis C virus infection in patients in whom the etiology of persistently abnormal results of liver-function tests is unknown</a>
<a href="http://www.natap.org/2005/HCV/090505_13.htm">Reemergence of Hepatitis C Virus after 8.5 Years in a Patient with Hypogammaglobulinemia: Evidence for an Occult Viral Reservoir</a>
<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16144125&query_hl=1&itool=pubmed_DocSum">Occult viral hepatitis and noncirrhotic hepatocellular carcinoma</a>
<a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1091708">Compartmentalization of Hepatitis C Virus Genotypes between Plasma and Peripheral Blood Mononuclear Cells</a>
<a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=415836">Hepatitis C Virus Persistence after Spontaneous or Treatment-Induced Resolution of Hepatitis C</a>
The term "occult" means "hidden", so in that sense occult hepatitis C is any form that is not detectable in today's "traditional" manner (i.e. - serum assay). So "occult" could be applied to either spontaneous clearer's or those who have already treated. And it could also apply to forms of compartmentalization. So in this sense it is a rather general term of use.
But, bottom line for patients is whether or not they have any from of remaining negative-strand (NS) HCV RNA in their systems, since this is the best indicator of any type of active viral replication taking place.
So any news - be it of patients who have treated or not - that finds evidence of replicating negative-strand HCV RNA is troubling, at best. The potential consequences are currently poorly understood, but relapse due to severely compromised immune system is a possibility. Also, long-term potential consequences from low-level infection/replication in terms of such things as liver damage and liver cancer are unknown. For example, if a Stage 3-4 patient obtains SVR yet remains NS positive - should there be more concern and monitoring in regards to this persons potential higher odds of HCC and/or further liver damage? (or less and/or slower healing of the liver due to occult)? And what about the ongoing sub-clinical infection's non-hepatic effects? Is the immune system still somewhat compromised as a result? Can this continue or trigger auto-immune response? etc.
There are innumerable questions related to occult - almost none of them good. And at this point few are answerable.
While SVR is today's ultimate tx goal - and for all of the wonderful benefits that can come with it - it does not necessarily spell the complete end of infection - nor concern.
If anyone is stage 3, or 4, and achieves a SVR they still need to be monitored for the development of liver cancer. Once you reach that level of fibrosis your are at increased risk of developing HCC. A CT scan, or ultrasound (hopefully both), along with blood tests yearly could be life-saving.
AS a stage 4, i agree with you. Just would add a upper gi yearly
some of these articles seem to have a recent date, but I remember reading them before, odd. I remember Castillo et al from an article on persistence last year, how do they show up again as new articles?
anyway, I always like to read these articles after a discussion on persistent HCV:
while some folks might be harboring some strands that might or not effect any response in their bodies. others can safely say they are cured!
Thanks so much for the links. There is quite a bit of reading there my friend. I read the Radkowski study when it was first published but the editorials are brand new to me and I appreciate you posting this stuff. Mike
I gotta agree with you there old friend. I remember when before I started this HCV & transplantation journey I subscribed to the theory that it was smart to "prepare for the worst" believeing that somehow one could get prepared. But I learned that you're never prepared for the worst no matter how much you think about it and no matter what you do to convince yourself that you're ready. When the worst comes no one's ever ready. So enjoy life now as best you can and don't look too far down the road and if, by chance, the worst comes you'll deal with it then. Hey, I'm SVR and I love it! Mike
Scott - I'm truly sorry you've been given this new challenge to deal with. As best I can tell, you're a pretty fierce fighter - now's no time to give in.
All - interesting discussions. This morning I had blood drawn for my yearly physical, and finally requested an RNA quant. As some of you will recall I finished tx over two years ago and refused to test at the time. I found tx (geno 1, 48 weeks) a thoroughly miserable experience and was interested in (1) putting my life back together (2) determining on a purely subjective basis whether tx had improved the time I had left to live: could I tell that life was better regardless of what the tests said.
I won't have the results for a couple of weeks and so my outlook is still uncontaminated by objective results. I thought I'd share a few impressions/prejudices I've picked up along this path.
- overall I feel something has "gone" and would guess the test will show SVR. The waves of fatigue and disorientation that were common before tx now seem very rare.
- the meds do more damage than Schering/Roche or your Dr. will tell you. On a biochemical level, they are quite crude and amount to revving your body in a hyper anti-viral mode for far longer than your body would ever maintain on its own. As best I can tell, there was no major damage from that year, but I feel as if it aged me about five. The effects did not fade for at least 18 months. Short term memory and language-specific cognitive function degraded much faster than per normal, age-related, deterioration.
- HCV is a wily enemy. The goal of tx is not its complete eradication, which is impossible with current technology, but reaching a new equilibrium point between your immune response and the virus, in short to lessen the chances of a premature death from ESLD or HCC. Regardless of how much low-level replication continues in various cell types ( and I do believe Radkowski's PCR data) the full-blown HCV-producing factory in the liver gets shut down or at least severely disabled.
- our ignorance is vast. Despite good progress, most of us will be long gone before any understanding issues such as extra-hepatic symptoms or even a simple detailed trace of RNA packaging affect clinical practice.
- this forum is the single best antidote to the virus or to the effects of tx.
there you are willing! I thought you had move your date from Feb to April! so now we wait for the confirmation of that svr. is it the qual or quant?
as for the cognitive effects, it worried me that a state similar to what appeared during tx in regards to memory and language had emerged months post tx, so, I began taking acetyl l carnitine. it has been studied in relation to alzheimer's and stroke, so what could I loose? after a month, I must say that something is finally "clearing" in my head, it feels subtle, but very noticeable to me, as I am recalling the proper words quicker as well as remembering things better. It could be the combo of this supplement and Sam e, or just it by itself. Worth researching.
Great links and great discussion. This is what I love about the forum. Lots of input, analysis, feedback, and opinion. We are all learning a great deal about the virus, even though there are many unanswered questions, and we are learning to balance uncertainty along with a positive approach to life, and a healthy appreciation of our SVR status, (whatever it does and does not involve).
As someone suggested yesterday, we should encourage the HCV doctors and professionals to visit, and absorb the content on this forum. It would provide them with better perspective, prod them into asking more questions, and demonstrate that the 'average' HCV patient might be a bit more sophisticated than they realize!
Excellent discussion....and WOW...no 'hotheads'!
OK, so I lied, so I am not entirely 'retired' from the forum yet.
The impressive list of ' viral persistence' related research articles just demonstrates how complex and unknown this virus really is. Anyone who really thinks it is just a liver and blood virus, and that when you treat with interferon/riba, and become SVR, it is cured, is seeing only a very narrow, simplistic slice of the real, multifaceted behaviors and ramifications of HCV. I think this is a subject that has probably just begun to unearth the 'tip of the iceberg' as far as what HCV is really all about. We know almost nothing about what might really be going on with HCV in the brain, bone marrow, CNS, organs and organ linings, connective tissue, lymphatic system, eyes, and on and on. Since we know almost nothing about these issues, the medical community for the most part just focuses on the obvious: liver infection (since it is a preferred site, and causes eventual death), and the blood, since it is so readily measurable and detectable.
I keep an open mind, and would love to believe in total eradication.....but I keep seeing all those red flags waving like crazy....in those thirty or so articles! Its hard to honestly convince myself that HCV is really only in the blood and liver....and then ..poof...its gone! There are too many extrahepatic issues, too much peripheral damage, too many studies, too much RNA evidence mounting, that lead me to suspect that the virus might just be more adventurous than most have ever imagined. I'm thrilled that SVR seems to quell the liver deterioration, and resolve , in some cases, some of the overall symptoms of HCV....but I still think there is more going on than meets the eye....and in time we will all have a much more accurate understanding of how the virus works. Maybe, just maybe, we will see treatments that address ALL of the modes of action that HCV employs. If it does 'lurk' in remote areas of our bodies, maybe medicine will find a way to disarm or destroy it.
I am happy to be in the 'cured as possible' camp, for now...but I will sure be watching for ongoing developments.
Willing: Thanks for the really nice support data contained in the articles you linked. This list of studies will bring everyone up to date on the 'persistence' subject, and will no doubt provoke ongoing discussion and debate. Glad to see you stopping by. My very best wishes on your PCR. Please let us all know the results. I'm betting you are 'good to go!'
wow Snook, sorry youre feeling poorly, but in all my nosyness in asking people about their experiences, what I get is that many many people have post tx sides anywhere from 3 months (if they are lucky) to 6 months, and a year is pretty common in my crude little research...I know you eat right and take supplements, you know that Califia felt much better once she got started replacing Vitamins, especially B12, turns out the meds gave her a big defiecincy...hope you feel better soon and I know you will...
on another note, I kept on hearing about hair loss and how people taking Biotin were saying it helped on treatment, etc. so I just started taking it for the heck of it, and you know, my hair is coming in thicker, I can tell the difference, it was kinda thinning a bit...guess the stuff works, at least for me...pretty cheap too...
Sorry I came into this so late -- and admittedly unprepared as I have not had time to go over the studies posted -- but I did want to get this question/thought in before folks disappeared into the night.
My understanding on occult/hidden virus is that as of now, no definitive studies exist which suggest the virus is replicating, as for example the virus in our bodies before we SVR. And according to my hepatologist, if it's not replicating then it's not going to do any harm -- or at least nothing suggests it will. Sort of like debris on a battlefield after all the bad guys are killed off.
If anyone has anything that suggests otherwise, please post as this subject is of great interest to me.
Good luck Willing with your PCR! Given I believe your enzymes are still in the normal range, I don't think you have anything to worry about -- plus you seem to handle things better than most of us anyway.
yeah, I agree with you there, I love the exchange of info and ideas, though I'm not quite as hopeful re the medical community reading HCV forums, although I do like the points Pretty made...in my experience I was always thankful if a doc of mine just kept up with current studies! I know they are soooo busy, but you'd think that most of them would be a bit more enthusiastic about researching out current info, trials, etc...guess the HMO's and such has put a big restriction on their time schedules...another reason to be thankful for these forums and the doggedly analytical patients that you find here and elsewhere...like you fer instance!
Another thing, isn't it great that this forum has been so even-keeled for what seems like months and months! I remember just ghost reading here a few years ago, and I didn't venture sticking my toe in here it was so combative...always enjoy lively debates but if it gets too vicious might as well stay on the LA freeways if I want that kind of stress...I get your point about the absence of hotheads...glad you still provide us with your valuable info when you can...
"the meds do more damage than Schering/Roche or your Dr. will tell you. On a biochemical level, they are quite crude and amount to revving your body in a hyper anti-viral mode for far longer than your body would ever maintain on its own. As best I can tell, there was no major damage from that year, but I feel as if it aged me about five. The effects did not fade for at least 18 months. Short term memory and language-specific cognitive function degraded much faster than per normal, age-related, deterioration."
Man, I couldn't agree more with that statement. I'll never forget the HONEST answer I got from Schiff during a consultation at week 42 about extending.. He said, there are more risks than benefits!!
I went in to tx at only 26 years old, and feel like I came out about 35-40 maybe? Post tx, although I obtained the SVR title, I suffer greatley from increased joint pain, mental disorientation, and fatigue..
I will do my best to answer your question, even though the answers out there are very 'grey' at best.
The 'Occult thing' we should place on the side for now, because it does not pertain to our HCV tx'ers or SVR's, but only to those oddly infected people with ongoing liver HCV replication, but no blood infection. Nobody really knows what or why that exists as of yet.
The other item, (which is sometimes mistakenly referred to as Occult virus) is usually referred to as 'residual persistent HCV', or 'persistent virus after SVR', or some similar title.
This 'persistent virus' if it exists, as many researchers claim,
has been found in various blood components, and organs (there is much controversy among the researchers as to the validity of these studies), and in some SVR's studied, the HCV low level RNA has been found in those more than 12 years SVR. The implication from the researchers is that the low level virus (in the PBMC, lymphatic system, and possibly CNS, spinal fluid and brain, etc ) must be replicating, albeit at very slow, and low levels.
Now, the fact that your doctor does not believe that there is any replicating virus remaining after SVR is very much 'par for the course'. Almost all the HCV doctors believe that the persistent virus research is flawed in some way (though they don't seem to say exactly how or why it is flawed), and that HCV just cannot exist and replicate independently of the blood and liver.
This is where many of the researchers seem to be on a diverging path from the practicing HCV doctors. There are also SOME researchers that also agree with the docs, and seem to find NO replicating virus after SVR, while a good handful of other research teams continue to find evidence of HCV replication, both pos. and neg. strand, long after SVR, in various organs and blood components.
I have given up trying to make sense of it, for the time being....there is just no real consensus, and there is not a lot of interest in the subject. I do not think the drug companies want to go anywhere near the issue...its easier to let everyone feel 100% confident that their medications are 'curing' the virus. I still wonder why the national liver associations are now saying that successful treatment will lower the HCV viral levels to undetectable, rather than saying eradicate, or cure. They must be concerned about some sort of mis-statement or inaccuracy.
Anyway, the above is my best interpretation of the current controversy, and state of affairs regarding persistence.
me too, I'm not a monk, I eat a lot of foods, Greek, whatever, but I try to use a lot of veggies, fruits, in all that I do, I'm just thinking that the oatmeal youre doing is probably helping with the cholesterol too...I eat a bowl a day like I said with a little bit of maple syrup, berries and soy milk and cinnamon...good for the skin too, think I'm repeating myself here...I'm just glad you lowered your cholesterol though, you know, you keep a nice diet, maybe not quite as stringent but along those lines, you might end up not needing the meds...keep my fingers crossed anyway...
It is so important when introducing a topic like this to a non-medical audience, to point out that while some *preliminary* studies speculate on occult and/or persistent virus, most hepatologists do not believe that any replicating virus exists after SVR and whatever does exist presents no harm to the host. In fact, even the research advocates of occult /persistent virus claim no "clinical significance" in their findings. Sometimes when I read follow-up posts by folks, it doesn't seem that point has been made clearly enough.
Regarding the definition of "occult virus". Apparently you and THG define it differently. Yours def is quite specific, his inclusive of any persistent virus or viral elements after SVR in blood, plasma, tissue, etc. I just choose to use his definition as many of the arguments against occult virus as a real threat to us SVR's apply to both.
As you say, further research will tell more of the tale, but so far I think it's more of a fascinating, intellectual exercise and not something that anyone about to treat, currently treating or even someone post treatment should get the least bit worked up about. A lot of other real (and proven) problems out there such as the havoc the treatment drugs do to our bodies not only during, but after treatment. I'd say this is 1000 fold more serious than maybe a one chance in 1000 of someone relapsing after five years SVR. Snookman said he's 26 and now feels like 30-40. I went into treatment at 59 years old feeling like 40 and now I genuinely feel my age, maybe older.
Forsee chants: oh go eat some soba...
LOL. Can you believe they were out of UNI (Sea Urchin) tonight :(
Had to settle for a salmon/avocado roll with miso soup and edamame.
As you may have guessed, I was a big fan of Japanese food before treating but during treatment couldn't even look at it, as well as many other foods including just about all vegetables. It's kinda nice to see my old taste buds starting to reactivate. I can't attribute it all to the diet -- who knows the role of the lingering treatment drugs -- but my cholesterol dropped in three weeks from 150-170 to 125. That's the lowest I've ever been. My guess all the soy and fiber. Or is it the magical properties of UNI???
wow! that's great!!!! especially with your family history! man, you must be jumping all over your yakatori!!!! (get ready for the onslaught, he he he!) there's a reason that heart disease is hardly even a factor in Japan, till they come over here and eat our diets!
I'm mostly on the Meditteranean Diet which I've mostly always done, lots and lots of tomatoes and galic, olive oil, olives, veggies, some pasta (artichoke pasta is a favorite) beans, lots of fruits and nuts, almonds, sunflower seeds, dried cranberries, etc. though I throw Japanese in there when I can, man, do I miss Sushi!!! and you know, I'm eating wasabei capsules, I just thought I'd throw that in my regimen, supposedly the Japanese eat wasabei as a way to add digestion enzymes, and to clear the liver....hmmm, sounds good anyway, ha ha!
I really liked the way Kalio said that those smoothies were helping her with sores and stuff while on treatment, I tend to keep those up on treatment, with my FAVORITE.....GOATS!!!!!!
I really like (or used to :) ) all foods. The good, bad and the ugly. Med foods were also one of my favorites but with the GERD and all, tomatoe based products, some med seasonings and a lot of fruit just don't work. The good thing about Japanese food is there's no milk or wheat -- or really mch fruit for that matter. As to Wasabai, I go light -- again because of the GERD. You're right about little heart disease in Japan -- but hypertension is rampant from all the salt they use. I now order the edamame (steamed soy beans) w/o salt.
Regarding the cholesterol, I don't think I will be able to keep it at those levels long term and I still feel a significant part of the lowering is temporary because of the treatment drugs. Unless I surprise myself, Statins or another cholesterol type drug is in my future. And while I don't relish any more drugs, statistically, this is probably more important for me than having treated for Hep C.
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=42&itool=pubmed_docsum">Hepatitis C virus persistence after spontaneous or treatment-induced resolution of hepatitis C</a> from 2004 to present <br>
<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=16611276%5Bpmid%5D">(1) Effect of anti-viral therapy for occult hepatitis C virus infection</a><br>
<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=16530526%5Bpmid%5D">(2) Hepatitis C virus core protein is a potent inhibitor of RNA</a><br>
<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=16511757%5Bpmid%5D">(3) High rate of spontaneous negativity for hepatitis C virus RNA after</a><br>
<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=16464222%5Bpmid%5D">(4) Cryptogenic cirrhosis and NAFLD: Are they related?</a><br>
<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=16447262%5Bpmid%5D">(5) Therapy of hepatitis C: From empiricism to eradication</a><br>
<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=16441471%5Bpmid%5D">(6) Long-term follow-up of chronic hepatitis C patients with sustained</a><br>
<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=16454708%5Bpmid%5D">(7) Understanding human immunodeficiency virus type 1 and hepatitis C virus</a><br>
<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=16416186%5Bpmid%5D">(8) Effects of combined antiviral therapy on asymptomatic mixed</a><br>
<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=16183410%5Bpmid%5D">(9) Hepatitis C virus-associated glomerulonephritis without hepatitis C</a><br>
<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=16251811%5Bpmid%5D">(10) Emerging evidence of hepatitis C virus neuroinvasion</a><br>
<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=16122975%5Bpmid%5D">(11) Evaluation of three commercially available hepatitis C virus antibody</a><br>
<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=15651757%5Bpmid%5D">(12) Long-term follow-up of HIV-infected patients with chronic hepatitis C</a><br>
<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=15894587%5Bpmid%5D">(13) Increased Fas ligand expression of CD4(+) T cells by HCV core induces T</a><br>
<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=16144125%5Bpmid%5D">(14) Occult viral hepatitis and noncirrhotic hepatocellular carcinoma</a><br>
<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=15914850%5Bpmid%5D">(15) Continuous release of hepatitis C virus (HCV) by peripheral blood</a><br>
<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=15939788%5Bpmid%5D">(16) Immune evasion versus recovery after acute hepatitis C virus infection</a><br>
<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=15858018%5Bpmid%5D">(17) Compartmentalization of hepatitis C virus genotypes between plasma and</a><br>
<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=15722526%5Bpmid%5D">(18) Mitogen-induced upregulation of hepatitis C virus expression in human</a><br>
<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=15854885%5Bpmid%5D">(19) Is hepatitis C virus infection of dendritic cells a mechanism</a><br>
<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=15838801%5Bpmid%5D">(20) Evidence for viral persistence in patients who test positive for</a><br>
<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=15763322%5Bpmid%5D">(21) The anhepatic phase of liver transplantation as a model for measuring</a><br>
<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=15777565%5Bpmid%5D">(22) Acute hepatitis C: diagnosis and management</a><br>
<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=15831916%5Bpmid%5D">(23) Hepatitis C virus replicates in peripheral blood mononuclear cells of</a><br>
<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=15766571%5Bpmid%5D">(24) HCV core protein localizes in the nuclei of nonparenchymal liver cells</a><br>
<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=15578396%5Bpmid%5D">(25) Prediction of relapse following treatment for hepatitis C: Is whole</a><br>
<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=15731994%5Bpmid%5D">(26) Acute hepatitis C: A multifaceted disease</a><br>
<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=15738952%5Bpmid%5D">(27) Immunology of hepatitis B virus and hepatitis C virus infection</a><br>
<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=15690477%5Bpmid%5D">(28) HCV persistence: Cure is still a four letter word</a><br>
<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=15619235%5Bpmid%5D">(29) Persistence of hepatitis C virus in patients successfully treated for</a><br>
<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=PureSearch&db=pubmed&details_term=15703689%5Bpmid%5D">(30) The immunologic basis for hepatitis C infection</a><br>
since hcv persistence is a regular topic of speculation I thought it would be interesting to check up on where the research has been going. The original major persistence paper is <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15140984&query_hl=42&itool=pubmed_docsum">Pham, et al 2004</a>. In the post above are the 30 journal articles that have cited that paper to date. It's likely that anyone publishing research in this area would cite the original finding, so I believe the above list should give a pretty good snapshot of where things stand today.
I haven't had time to dig through this pile in any detail yet, but here are some thoughts:
- noone has challenged the validity of the Pham/Radkowski plus-strand RNA detection ; that much seems accepted
- minus-strand is much harder to detect (it only exists as a brief intermediate while a virion is replicating). Since we're talking about small amounts of residual plus-strand, detecting the associated minus-strand seems far beyond the reach of even the most sensitive PCR.
- the plus strand RNA wouldn't be there unless the virus was replicating; however no associated clinical manifestation has been reported yet.
If anyone has time to read through these and finds anything more alarming please post!. Also, the recent Pardo et al (1) in the above list defines <em> "Occult HCV infection is defined by the presence of HCV-RNA in liver cells but with undetectable anti-HCV and serum viral RNA". </em>
Thanks for all the good wishes - I'll post my results - and Cuteus thanks for the acetyl carnitine tip, I'll investigate. You see what I mean about defective language processing, I missed that conditional "would" in Scott's post. I'm much relieved - he probably is even more so.
As far as definitions go, I think that negative-strand found in PBMC's might well be considered "occult" - thereby moving the definition beyond only the liver. This seems to be what <a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=415836">Pham et al</a> suggests.
Radkowski's study is pretty strong evidence for occult/persistence existence. Even in <a href="http://www.natap.org/2005/HCV/010305_04.htm">Alter's rebuttal editorial</a> he doesn't dispute the presence of occult, just whether or not there is any clinical significance:
(from the rebuttal)
<i>Importantly, 9 of 11 patients with follow-up biopsies showed significant improvement in necroinflammatory and fibrosis scores <b>despite the presence of residual virus</b>.</i>
<i><b>This residual low-level replicative state</b> may not have clinical relevance since there is coexistent histological improvement and maintenance of a strong humoral and cell-mediated immune response that should hold the virus in check.</i>
The most recent paper I saw was <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16611276&query_hl=1&itool=pubmed_DocSum">(Pardo et al)</a>, which defines occult as being in the liver - though all of the subjects present PMBC RNA positivity (but the abstract doesn't say if it's negative-strand or positive strand that they tested for). 24 weeks after a 24 week tx, 30% remained PMBC positive. Of the 5 who underwent follow-up bx, 100% remained liver RNA positive. SVR was obtained in 30% (though I'm not sure how they are defining SVR, given that all of the patients tested serum clear pre-tx. Another short-coming of the abstract is that we are not told genotype. And we're not told how the decision to tx for only 24 weeks was reached).
On the face of it this study looks pretty damning, too, in terms of persistence/occult - most especially in the 5 out-of 5 liver positivity.
Glad to hear you're doing better. I'll be keeping an eye out for your soon-to-be SVR news, too.
DD: We know almost nothing about what might really be going on with HCV in the brain, bone marrow, CNS, organs and organ linings, connective tissue, lymphatic system, eyes, and on and on...but I keep seeing all those red flags waving like crazy..There are too many extrahepatic issues, too much peripheral damage, too many studies, too much RNA evidence mounting, that lead me to suspect that the virus might just be more adventurous than most have ever imagined..but I still think there is more going on than meets the eye..
Wasn't it only last week that you making similar conjectures about the treatment drugs as opposed to occult/persistent virus?
How many complaints have we read here and elsewehere about tx-induced memory loss, eye problems, joint and connective problem, post-tx depression, etc?
I do agree with the last sentence but based on current evidence would like to believe that any residual manifistations of hep c beyond SVR are somewhat insignificant compared to the residual effects of the treatment drugs themselves, not to mention other health issues most of will face as we become older. Remember (and that's getting hard for me post tx :)) -- all these articles appear to state that so far no clinical significance has been found with occult/persistent virus. I do know a lot of people objected to the social/political significance of that army study posted recently. But the one thing that did strike me was that those untreated for hep c seemed to fair about the same as the general population in regard to hospitlizations and overall health.
It's great that we have so many researchers currently working on the subject of occult/persistent virus -- but how soon do you think it will be when we will be able to post here the same number of articles on the long-term effects of combo treatment? Which drug company will step forward first to fund it. LOL.
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