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New Pham paper re: Occult Hepatitis C

by TnHepGuy_, Feb 12, 2008 08:08AM
"Hepatitis C Virus Replicates in the Same Immune Cell Subsets in Chronic Hepatitis C and Occult Infection."

"BACKGROUND & AIMS: Infection of the lymphatic system by hepatitis C virus (HCV) appears to be an intrinsic characteristic of chronic hepatitis C (CHC) and low-level (occult) HCV infection, but the subsets of immune cells involved were not defined. The aim of this study was to characterize HCV replication status and to assess virus compartmentalization in CD4+ and CD8+ T lymphocytes, B cells, and monocytes in CHC, and silent infection persisting after resolution of hepatitis C. METHODS: Immune cell subtypes isolated from 7 patients with CHC and 7 individuals with occult infection were analyzed for HCV-RNA-positive and -negative strands and, in selected cases, nonstructural protein 5A display and HCV variants. RESULTS: All subtypes of immune cells investigated support HCV replication in both forms of infection, although significant differences were found between patients, and virus loads in the cells were greater in CHC than in occult infection. Although HCV RNA occurred at a comparable frequency in all cell subtypes in CHC, monocytes contained the greatest loads. In contrast, B cells tended to carry the highest virus quantities in occult infection, whereas monocytes appeared to be the least frequently infected. Detection of HCV nonstructural protein 5A and HCV variants that were not found in plasma confirmed virus replication in different immune cell types. CONCLUSIONS: This work documents that the immune system supports HCV replication regardless of clinical appearance of infection and identifies immune cells that are reservoirs of HCV in symptomatic and occult infections."


TnHepGuy
Member Comments (43)

by TnHepGuy_, Feb 12, 2008 08:10AM
Here's the link to the paper:

http://www.ncbi.nlm.nih.gov/pubmed/18243182?dopt=AbstractPlus


TnHepGuy

by Ginger12521, Feb 12, 2008 08:34AM
To: TnHepGuy
This is one topic that makes me sit back and say hummm? I have to wonder if everyone in the U.S. got tested for occult HCV, how many would indeed be reactive with a positive PCR?

I suppose there's no way to know unless everyone recieved a liver biopsy and tested it for +PCR RNA.

Crazy virus to say the least!

Thanks for the article.

by DoubleDose, Feb 12, 2008 09:21AM
To: TnHepGuy / Everyone
Thanks for the up to date information, on a subject that we have been discussing a good bit lately on the forum.  This is exactly why I have long had concerns about 'atypical transmission',  symptoms in close contacts, and also have hypothesized that the reason so many 'alcohol abusers' seem to develop HCV, in spite of not having other risk factors, might just be that many people already 'carry' an undetected, non-blood form of the virus, in a somewhat dormant, or carrier state.

  If there is truth to this immune system low level infection, then I could not imagine why it would not be able to also replicate in similar tissues and cells in almost anyone.  My take is that the researchers now need to look at two groups, and determine what the percentage of positive HCV infection is within immune and lymphatic cell structures among these groups.  Those groups would first be those close or intimate contacts of persons who have had true, blood borne, chronic HCV infections.  The second group would be the general population, in order to see what the real rate of 'underlying immune system HCV infection' might look like.  It could be on the lower side, like 2% (reflecting chiefly those who also concurrently have the full blown CHC infection,  or even up to 5% or 10%, reflecting mostly those infected AND their close contacts, etc.  Or, there could already, over the many hundreds of years, be a large percentage of the population that has become a 'silent carrier' of this lymphatic form of infection. (as are many other  viruses...EBV, HPV, HSV, etc.)  Who knows, this could be present as Ginger stated above, in much of the population.  

The first thing they need to absolutely determine though is this:  whether this form of infection is able to exist in those who have never had the full blown HCV chronic blood liver infection.  They need to test for this 'lymphatic infection' in those who have absolutely no viral load on PCR testing in the blood, and no reactivity to the HCV antibody test using the typical blood testing.   If it turns out that there are populations out there harboring ONLY this 'silent' form of HCV infection, then we have an entirely new ballgame.  We would then need to learn what this form of infection might do, or what problems might develop, and also to understand what, if anything, could provoke this low level, in-check, immune system infection to cross over the humoral immune system barriers, and become a chronic HCV blood borne infection.  I want to know more about this subject, and I bet the researchers are really whetting their appetites after these study findings.  We learn more every year about HCV!

DoubleDose

by TnHepGuy_, Feb 12, 2008 03:40PM
To: DD
Yes, some of the questions that get raised in my mind re occult are:

The current assumption is that the virus is assumed to be 'controlled/contained' via the immune system. If that's the case, then by definition it (the virus) is generating an immuno-response. And more to the point, it's generating a chronic immuno-response to maintain containment. The question then becomes what systemic negative effects (if any) might this constant immune stimulation/response lead to?

Also, how many other low-level 'contained' viral infections (be they hepatitis or non-hepatitis) might each of us have? And are they generally considered benign - or might each 'ramp-up' the immune system in it's own particular manner, thereby leading to potential long-term damage and/or other concerns?

And of course, how much is anyone with any form of occult viral infection at risk for viral rebound should the immune system become compromised in any fashion (e.g. - through immuno-suppressants, auto-immune concerns, age-related immune issues, etc)?


TnHepGuy

by DoubleDose, Feb 12, 2008 05:01PM
To: TnHepGuy
Those are exactly the questions on my mind!  This idea of viral containment to me generates a picture of an immune system constantly churning and reacting, which in turn would have a huge potential to create some sort of 'autoimmune' disturbance or illness over the long term.  At the very least, it would seem to create a chronic immune system adjustment that would not be very normal.  Each virus under containment would probably have a particular profile, and level of 'effort' necessary for the immune system to effectively deal with it.  The greater the number of latent, chronic viruses, and the more potent and aggressive of the viruses pushing on the immune system, would provoke the greatest level of bodily and systemic reactions, I would think.  

I wonder if any of this could play into the underlying causes or mechanisms for cause-undetermined illnesses like CFS, Fibromyalgia, or even Sjogren's, and other autoimmune