A study on HCV Cellular Immune Responses and non-serum transmission implications

[DoubleDose]

Here is a study I came across that addresses one of my ongoing concerns, and a concern that HR addressed in response to some of my recent thoughts.

It is a wordy study, but was done with tremendous attention to detail, using a variety of very specific tests.  Basically what they conclude, is that people in CONTACT with those who are HCV Positive have a very high probability of developing ongoing cellular immune responses to HCV.  Their conclusions are interesting, and are framed as either/or type scenarios...one of which says the individuals were exposed to the virus, but fought it off and now retain the cellular immune responses in tissues and organs.  The other scenario is that they have an ongoing, low-level HCV infection in these tissues and cells, that stays under the antibody test and PCR testing radar.  In other words, they are infected, but are not detected on standard testing.

This is a potential reason for my feeling that I have observed 'HCV-like, extra- hepatic symptoms in many of my past close contacts and family members...even though they test negative on standard HCV antibody tests.  There may actually be a low level chronic, but undetectable infection!  OR, according to scenario #1, there may just be ongoing cellular immune responses, without any HCV present.  Maybe this also could provoke ongoing symptoms in  these close contacts.

Here is the study.  Please take the time to read it fully and patiently.  It is fodder for much thought.  And it confirms many of my long held concerns!!!

http://www.ajtmh.org/cgi/content/full/73/1/44

Comments????

[Lara_X]

I don't know if I have hep c or not... I'm not getting the antibodies or not getting them to the detectable level, not sure. But I have been having symptoms that indicate liver disease and I'm trying to educate myself about these things.
DoubleDose, thanks for sharing all this info. It is relevant and useful. My opinion was confined to the first article you urged us to read though. Everything else you posted is true and needs to be known.
It sure helps that research never stops questioning, that's how we progress. On the other hand, unless you are a researcher yourself or extremely interested in your disease, I'm not so sure non-stop questioning and worrying does you good. I do believe that if you achieve SVR status and you learn to manage your disease the best you can you should try to live your life and enjoy your family as much as possible under the circumstances. I'm not saying you shouldn't get informed about possible outcomes and risks, but you have to keep your mental balance and take from them what helps you in your fight both physically and mentally. And this comes from someone like myself who IS a worrier.

[MissMiss]

On the one hand, I hate this kind of talk because it seems some have gone on to obtain "regular insurance" after a few years of SVR and I was hoping we all could be considered virus free and be entitled to insurance without stipulations.

On the other hand, this is info we all need to know and understand.  If you look at the HCV virus itself, there are already many genos and sub-genos identified.  I do remember a couple here stating theirs could not be identified.  In the back of my mind, I always wondered if those not specifically identified might be what you are talking about.  

I just think it would be irresponsible for anyone to assume we have identified all genos, etc in any virus.  (I watch and read sci-fi, viruses are always mutating, lol)  Seriously, I read other stuff too.  It makes sense that the virus would change somewhat when inhabiting something other than blood.  And look at the herpes virus that sits dormant for long periods of time until something triggers it.

I, for one, appreciate any research you come up with.  Thanks.

miss

[DoubleDose]

I think you are on the right track.  I believe that there may be a slightly different form of the virus, which may inhabit tissues, mucous membranes, sexual organs, gastric mucosa, etc.  This may be responsible for the Cellular Immune Responses found in the study.  Also, there needs to be more research to see if this indeed is happening, and if there is any pathology involved, or any potential for long term physical effects.  Also, could this 'benign' or non-serum version of the virus eventually trigger a full blown infection under the right circumstances?

There is much more to be learned regarding HCV and all its ramifications.  Even in SVR's there seems to be a lot of speculation about what forms of infection remain, and what the consequences might be down the road.  Very few answers at this point.

Transmission issues may be more complex, and less easily detected than once thought.

DoubleDose

[DoubleDose]

These symptoms do not strike me as hepatic either, but of course they would not be hepatic, but more extra-hepatic.  As in many who are HCV+, the symptoms experienced are often broken into either 'hepatic' or 'extra-hepatic' in nature.  Extra-hepatic symptoms common to those infected with HCV range from Sjogren's-like or sicca syndrome, to extreme fatigue disproportionate to liver damage, and diabetes, to depression.  All well documented HCV extra-hepatic symptoms.  There are a host of conditions being explored that may be caused by, or accelerated by HCV, all unrelated to 'hepatic' issues.  You see, HCV is much more than just a liver virus, and you will find current literature from the AASLD describing HCV as sialotropic, lymphotropic, immunotropic, arthrotropic, etc.  The suymptoms I described are very much in-line with typical HCV extra-hepatic sx.

Here is an exerpt from a pub-med article:

CONCLUSIONS: A major subset of HCV-positive patients with definite subjective sicca symptoms and positive objective tests may indeed present a true, though peculiar, subset of SS.

There are strict similarities with key clinical, pathologic and immunologic findings of definite HCV-negative SS. Other features appear more characteristic of HCV infection. When also considering that HCV is sialotropic and may be treated, HCV-related chronic sialadenitis represents a unique opportunity to clarify key pathogenetic events occurring in the large majority of HCV-negative SS; and similarities to typical primary SS, rather than differences, should be taken into account.

PMID: 12516900 [PubMed - indexed for MEDLINE]

Here is another:

Matthew Dolan, citing several studies in his book The Hepatitis C Handbook, backs up this claim. Dolan points to a study by Christian Stassburg and Michael Manns in Viral Hepatitis Review that noted:

[MissMiss]

Could it be that the virus we may (or may not) be sharing with family is slightly different.  I mean, if it shared by touching, mucuos, anything but blood, maybe there is one slight change in that virus, thus they don't get a full blown viral infection.  A mutation, if I may.

HR mentioned the fella they knew was sleeping with his wife because of her blood levels.  I don't think this is something to ignore but honestly, at this point, there isn't a whole lot we can do about it until there is more research done.  

Thanks for sharing this.

miss

[DoubleDose]

Maybe I should be called upon to build that control group.  Sacrifices, sacrifices!

DD

[Lara_X]

I have read the article and in my opinion it strongly suggests that yes, anti-hcv negative household contacts MAY have been exposed to the virus, but that CMI has helped them clear the subclinical infection, either because it was a small viral load they were exposed to or because their immune system did its job properly. The authors clearly demonstrate the idea that CMI proves a resolved infection and NOT "a healthy carrier state with the virus being present in some body compartment" : "We speculate they are often low-dose exposures stimulating HCV-specific CMI that ABORTED, or rapidly CLEARED, the viremia".

As for the symptoms you describe, they could be caused by anything, and to me they don't necessarily seem as "symptoms compatible with hepatic disease" per se.
I'm not saying anti-hcv positive people should not care about possibly infecting their families and partners, but at the same time becoming paranoid about sharing your household with your family members is not a good idea either. Such paranoia might do more harm than good to one's family in the long run.

[Skepsis]

I speculated myself about having afflicted my wife with such very similar symptoms.

But to get a scientifically founded unbiased answer I should have married some sufficient high number of wifes to be able to build a control group to treat with placebo certainly. But polygamy would be objected by both my wife and law (and all of my morals, as well) so I cannot provide any easy answer to this question... :-)

[Kalio1]

Well said, Lara. Life is filled with "what ifs" and unknowns, this info and research is interesting and valid however to remain overly focused on HCV after SVR seems detrimental to me. Granted, as you say, it is good to be cautious but these types of symptoms can be attributed to everything from anxiety to pollen or dust and do not strike me as hepatic in nature.

Welcome to the forum, are you a fellow HCV+ soul?

[DoubleDose]

I agree, that they do not directly implicate the cellular immune responses in causing any symptoms, or actual disease, but they do leave the door open to it causing a possible chronic infection, below the limits of detection.  This is the second of their two possible scenarios.  If so, it could be similar to what the SVR's experience, with residual HCV that is under the limits of detection, remaining in tissues and compartments after SVR.  

The systoms issue is one that I take lightly....when they say that HCV has no symptoms....we all know that the medical community has said this for years.  Doctors that I have met with have said this to my face.  I lived with HCV for decades, and I know that there are a multitude of symptoms.  I think the symptoms are often subtle, blamed on other conditions, and ignored by many doctors.  How many people with HCV have you known that did NOT have any symptoms.  I think it just becomes a 'catch phrase' that doctors use in describing HCV.

In this case I hope that I am totally wrong in my suspicions.  I am not at all happy about the prospect of the disease being able to transmit in 'atypical' ways, if it does, and would love to see this line of study proven incorrect.  I still have to wonder why it is currently the subject of a large study , and what some of these researchers actually suspect is happening.

I would love to hear feedback from others on the forum regarding whether they have seen any curious symptoms in their family members over the years.  Please do convince me that I am on the wrong track!  

DoubleDose

[Moniker]

Most of my friends and family have at least some of the symptoms you mention. I think these are very common symptoms, symptoms which those of us living in human bodies are familiar. Perfect health and well being are not so common, although I feel I'm approaching perfection now that I've achieved SVR. I feel fine and so does my family. My dog is the healthiest and happiest member of our family, but she is obsessed with chasing squirrels.

Bob

[jmjm530]

Moniker: Most of my friends and family have at least some of the symptoms you mention. I think these are very common symptoms, symptoms which those of us living in human bodies are familiar.
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Ditto. And congratulations again (unless I missed it the first time :) on your SVR!

[jboyhk]

If this was Nazi Germany it would be interesting to see if these children who have CMI to HCV are actually 'vaccinated' against HCV infection (like the article refers to the HIV cases) by intentionally infecting them.

If they are vaccinated then it seems possible to create one.

[DoubleDose]

The cellular immune responses were SPECIFIC to HCV.  In other words, they are immune responses ONLY caused by HCV, and they leave a 'footprint' that indicates HCV was there 'visiting'.  

There have been a couple of other small studies done that looked at cellular immune responses to HCV in close contacts, and they came up with similar findings.  Now we are waiting to see larger studies conducted, across a wide population of HCV+ individuals and their families, intimate contacts etc.  I have been given some preliminary information on a Untied States based study which is going to be initiated in the upcoming year, by a top Hepatologist at one of the biggest HCV research oriented medical centers.  I am very anxious to see what they find, and what they conclude that this cellular immune response might imply, and if there are any 'chronic infection' related ramifications.

I really think it is irresponsible for people to take the attitude that it cannot be a problem, because we have no proof that it exists, or that any symptoms observed MUST automatically be attributed to unrelated factors.  These are issues that nobody understands fully at this point, as evidenced by the comments in the linked article.  After seeing the amount of new, and contradictory information that has come to light in the last three years regarding HCV, SVR, persistence, other organ infection, etc....I would be the last person to just 'shrug off' this issue of 'cellualr immune responses to HCV' as not being important.  HOW can we know that?

DoubleDose

[avidreader]

There are so many things that we don't know or don't understand. I don't think anyone's suggesting that we 'shrug them off'--just that sometimes we really just don't know and won't know until someone brighter then us (or at least me) figures it out. I always find your posts interesting and enjoy reading them--you are well informed, but I too must point out that the list of symptoms you describe your friends and families as having strike me as very strong indicators that they are, indeed, alive and as well as can be expected given the stressors the human race has added to our planet.

[DoubleDose]

A comment from the study in the conclusions section:

None of the subjects with HCV-specific CMI responses had a history of hepatitis or symptoms compatible with hepatic disease. The majority of HCV infections are asymptomatic, even during the acute phase.2 Therefore, we speculate that our CMI-positive seronegative subjects had a transient very mild infection, possibly associated with low-dose exposure to the virus, which was cleared. Infection is supported by most of the immune responses being to non-structural epitopes of HCV, an indication of replicating virus. A less likely, in our opinion, alternative is the CMI positive individuals have a healthy carrier state with the virus being present in some body compartment (i.e., in the liver) and not in the blood or it is replicating at levels below the sensitivity of our PCR assay (100 copies/mL).



Although our data does not elucidate on how these exposures to HCV occurred, the results suggest they are underestimated in endemic areas using anti-HCV. They could be caused by a common exposure infecting multiple members of the household or they may be between the HCV-infected and non-infected within the household. A common exposure during intravenous therapy of schistosomiasis as occurred in the past11 is not a factor, as all but one of those having CMI in the absence of HCV antibodies were children born after treatment with tartar emetic was discontinued.

We speculate they are often low-dose exposures stimulating HCV-specific CMI that aborted, or rapidly cleared, the viremia. These exposures might be from shared toothbrushes or other toilet items. Could they be from exposures to and from cuts, nicks, skin abrasions, and ulcerations that children often have?

[jboyhk]

I still have problem understanding how from this article you can make the leap to hepatic illnesses. The article in no way suggests that (in fact it talks about the full blown disease being asympotmatic).

[cuteus]

how do we know that the cellular responses in this group was due to hep c and not other viruses native to the land? those responses are cause by hep c exposure only?

[cuteus]

what were they referring to when this was stated:
"Other common exposures (e.g., injections given to multiple members of the household using the same needles and syringes) could certainly be a risk. "
That statement came AFTER the one about the intravenous therapy.

[Kalio1]

I agree, the symptoms are far too common and can be attributible to any number common causes. Household dust or other environmental allergens or pollutants for instance.

[DoubleDose]

No, if you read the end of the study, the children they studied were born after the multiple syringe usage.  They discounted that whole line of potential infection.  AND, they are not talking about typical HCV blood infection, but a different form, based on cellular immune responses.  

Did you actually READ the study.  I am trying to make sense of this, not just shoot it down because it doesn't feel good to consider it.

Also, note the different test responses from those in the HCV positive families, vs. those in the non-infected families.  Close to 'zero'cellular immune responses, if there was no HCV positive person in the environment.  Not so, for the people in contact with an HCV positive individual.  A high rate was found!

Again, they DISCOUNT the use of syringes for causing this cellular response.  The study was done in children born after this practice was in use!!!  We have just not done these studies here in the US.

This same issue is the subject of an upcoming study by one of the nation's leading Hepatologists.  It is a serious issue, not one to be 'blown off', if you read the study.

Also, Hepatitis Researcher discussed this same issue several weeks ago, indicating an absolute possibility of 'cellular immune' responses within HCV contacts.  We just do not know the implications of this, or how widespread the phenomenon is!

AND NO, these are not all just common symptoms every household has.  Not by a long stretch!

DoubleDose

[cuteus]

isn't this the Egyptian study we discussed a while back?  where the HR group included people that could have been infected by multiple use of the same syringe among family members?
how does this confirm your suspicions?  
This looks like the same discussion we had a while back, when this study was first linked.  
If members could have been exposed to hcv via syringe use, and some recovered and others did not, how does this confirm infection via common contact between family members? After all, the researchers are filling the blanks with whatever response the family wants to share and they might not be sharing or admitting to doing treatments that were banned.

[jboyhk]

Those all seem like very common conditions that people in non Hep C households would get.

I don't know how you can make any connection.

[DoubleDose]

By the way, some of the symptoms I have observed in close contacts over the years include:

* increasing bouts of fatigue and sleepiness at inappropriate times

* abnormal forgetfulness or short term memory loss

*  arthritic and muscle related symptom development, especially neck, back, and hip related.

* development of dry eye, floaters, and dry skin. Eye problems, focus, etc.

* and ongoing 'allergic type condition' year round, characterized by sinus inflammation, throat clearing, irritated eyes, and a congested feeling.  This seems to be prevalent among all contacts!

*  mild balance issues, and gait disturbances when walking.  'Klutziness', dropping things, and bumping into things.

*  difficulty awakening in the morning, and non-refreshing sleep.

*  rashy outbreaks, sometimes on face, under eyes, or on trunk.

I am sure there are some I am leaving out, but if anyone else has observed any of these issues in loved ones, or family members, please do comment.  I have seen these symptoms develop in contacts of wide ranging ages, many under 40 years old, so I do not attribute any of this odd stuff to their natural aging.
Its all too similar!!!  Cellular Immunity to HCV????????

Comments?????

DoubleDose