Article on Occult/Persistence and Other Posts

[TnHepGuy_]

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>"

[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.