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Occult HCV discovered in intimate partners: a research study
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Occult HCV discovered in intimate partners: a research study

This article was forwarded to me by a forum member who also shares an interest in and active suspiscion regarding transmission of 'forms of HCV' to our intimate, sexual, and familial partners.  I find the article confirming of my concerns and a bit frightening in its implications!  As many of you know, I have always felt that I have seen similar symptoms in my current and past intimate partners (and several family members as well) to what I experienced from HCV.  The symptoms developed in them AFTER our relationships began, usually a few years after, and see to reflect the identical issues I was wrestling with.   Here is the research study.  I am sure there will be more in the future.  The implications are potentially huge, and could encompass large segments of our population. Note, these sexual partners were sero-negative for HCV on blood testing, thus APPEARED to be not infected by standard testing.  Thanks again to the forum member who sent me this article:

Occult HCV in non-HCV partners

Cellular immune responses and occult infection in seronegative heterosexual partners of chronic hepatitis C patients.
Roque-Cuéllar MC, Sánchez B, García-Lozano JR, Praena-Fernández JM, Núñez-Roldán A, Aguilar-Reina J.
Source

Grupo Sección de Hepatología, Servicio de Aparato Digestivo Hospital Universitario Virgen del Rocío de Sevilla Servicio de Inmunología, Hospital Universitario Virgen del Rocío de Sevilla Unidad de Metodología y Evaluación de la Investigación. Fundación Pública Andaluza para la Gestión de la Investigación en Salud de Sevilla (FISEVI), IBIS. Hospital Universitario Virgen del Rocío de Sevilla, Spain.
Abstract

Summary.  It is unknown whether hepatitis C virus (HCV)-specific cellular immune responses can develop in seronegative sexual partners of chronically HCV-infected patients and whether they have occult infection. Thirty-one heterosexual partners of patients with chronic HCV were studied, fifteen of them with HCV transmission risks. Ten healthy individuals and 17 anti-HCV seropositive patients, without viremia, were used as controls. Virus-specific CD4+ and CD8+ T-cell responses were measured by flow cytometry against six HCV peptides, situated within the nonstructural (NS) proteins NS3, NS4 and NS5, through intracellular detection of gamma interferon (IFN-γ) or interleukin 4 (IL-4) production and CD69 expression. Sexual partners had a higher production of IFN-γ and IL-4 by CD4+ cells against NS3-p124 (P = 0.003), NS5b-p257 (P = 0.005) and NS5b-p294 (P = 0.012), and CD8+ cells against NS3-p124 (P = 0.002), NS4b-p177 (P = 0.001) and NS3-p294 (P = 0.004) as compared with healthy controls. We observed elevated IFN-γ production by CD4+ T cells against NS5b-p257 (P = 0.042) and NS5b-p294 (P = 0.009) in the sexual partners with HCV transmission risks (sexual, professional and familial altogether) than in those without risks. RNA was extracted from peripheral blood mononuclear cells (PBMC), and detection of HCV-RNA positive and replicative (negative) strands was performed by strand-specific real-time PCR. In four sexual partners, the presence of positive and negative HCV- RNA strands in PBMC was confirmed. Hence, we found an HCV-specific cellular immune response as well as occult HCV infection in seronegative and aviremic sexual partners of chronically HCV-infected patients.

http://www.ncbi.nlm.nih.gov/pubmed/21914075

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By the way, I think this finding is actually kind of HUGE!!!  It adds a whole additional dimension to what we consider to be HCV Infection!!!  There may be LOTS more than meets the eye.  As I have alwasy suspected!!!!!

DoubleDose
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"I have always felt that I have seen similar symptoms in my current and past intimate partners."
If you believe that HCV is pasted so commonly during sexual relations why aren't you practicing safe sex?


Hector
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" Thirty-one heterosexual partners of patients with chronic HCV were studied, fifteen of them with HCV transmission risks."

" In four sexual partners, the presence of positive and negative HCV- RNA strands in PBMC was confirmed."

This will be huge news *if* the results can be duplicated in a larger study and a more rigorous set of controls is used. More than 4 out of 31 people lie about their sexual practices.
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Avatar_n_tn
And for balance on the other side of the coin, here is commentary from the 2005 EASL meetings and clinical presentations:    (their comments)

"Low levels of HCV exposure may also occur in family members of HCV RNA-positive individuals.[11] Similar to findings observed in individuals who have suffered needle-stick injury, there have been several reports of HCV-specific T-cell responses in anti-HCV-negative/HCV RNA-negative patients in the households of individuals with hepatitis C.[12] However, the significance of these data has been questioned because it is challenging to select an appropriate control group of unexposed individuals. A very elegant and comprehensive study was presented by Kennedy and colleagues[13] during this year's EASL meeting in which HCV-specific T-cell responses were studied in sexual partners of HCV-positive patients. This study involved 5 individuals with resolved HCV infection, 5 HCV RNA-negative sexual partners of HCV-positive patients, and controls without any evidence of HCV risk factors. T-cell responses were measured against 601 overlapping peptides spanning the entire HCV genome. It is interesting to note -- and is in line with previous reports -- that these study authors were able to detect HCV-specific cellular immune responses in HCV-exposed noninfected sexual partners. However, these T-cell responses were focused on much fewer peptides than in HCV-recovered patients and did not differ from responses detected in unexposed individuals. HCV peptides detected in sexual partners and unexposed controls had sequence similarities to proteins found in other common viruses, such as herpes simplex virus and human papilloma virus. Further investigation suggested that T-cell cross-reactivity between the different viruses and HCV may be responsible for the positive results seen in the initial screening study -- a phenomenon that we have described previously for HCV and influenza virus (ie, the host's response to an infectious agent is influenced by cross-reactive memory cells induced by past exposure to heterologous viruses).[14] The clinical significance of cross-reacting T cells in the outcome of patients with HCV infection remains to be determined; however, a very recent report from Italy suggests that cross-reactive HCV-specific T cells may account for the severe courses of acute hepatitis C in specific cases.[15] "


My comment:  This critique seems to indicate there is less of a concern about true infectivity from the exposure by sexual partners....  Let me know your interpretation of this piece above please......

DoubleDose
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Avatar_n_tn
even if you disregard cross reactivity "investigation suggested that T-cell cross-reactivity between the different viruses and HCV may be responsible for the positive results seen in the initial screening study"

what seems to be reported by Roque-Quellar et al is primarily heightened CD4+ and CD8* T cell to HCV specific  epitopes along with some PBMC-detected RNA.

This doesn't seem very surprising. If Joe-chronic-infection-Doe is cranking out an astronomical number of new virions/day, as predicted by hcv kinetics models, eg
http://www.nature.com/cdd/journal/v10/n1s/full/4401118a.html

some will obviously find their way, via semen, saliva, tears, sweat, etc. into anyone Joe comes in contact with. However, the main point is that low-level transient, HCV response does not constitute established infection.
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You just never know who is going to come out to post when DoubleDose cranks up the occult press!!!!  

Hi Willing, its great to hear from you!!  I hope you are right about this stuff not constituting 'established infection'....My concern, and I think some of the researchers as well, is just this:  What the heck does this stuff represent, in the studied close contacts...and might this not be some 'other' form of HCV infection, rather than traditional 'established' infection??  

If PBMC's are actually compromised in some contacts, and if the cellular immune responses prove to be permanent, and NOT just due to cross-reactivity...how are we certain that there is not an ongoing, localized, cellular infection...or even an 'occult' infection?  Maybe it IS in the blood, liver, nerves, salivary tissues, etc....but at levels so low it cannot provoke a full blown, classical, HCV blood borne infection.  

Just a few of my concerns.  I think the first article linked also mirrors these concerns to an extent.

I hope you are doing well and enjoying life Willing.  We don't see enough of you anymore...the board must be getting boring.

DoubleDose
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http://www.ncbi.nlm.nih.gov/pubmed/20648609

Have you ever had this series of blood markers run - and if so, where did you have it done?
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Avatar_m_tn
I have to wonder if it is present, how common is this?  Your experience seems to be different than most of the HCV positive people in a domestic partnership that I encounter.

You have to wonder if it is in the presence of other viruses.  Your studies do not discount this, if anything they may even allude to it.  

If the sexual partner is exposed to active HCV, by what mechanism does it stay "occult"?  One would think in the USA with increased IR which causes a diminished immune response that we might be more cases of occult or outright transmission.  If there are 3-5 million cases in the USA and this remains an unproven theory one might infer that there are few cases or the there are numerous unreported/ undiagnosed cases. If there were almost 200 million infected worldwide...... where is all of the data?  Wouldn't there be more?  Wouldn't here have been a lot of sick spouses of HCV positive patients?  Wouldn't some doctor have pondered that some time ago and made a connection?  Is it that these individuals don't seem to be sick, impaired, or suffer damage?  The studies don't seem to evaluate the health status of the partners.

And yes..... the studies are very small and I can't tell even that they were constructed so that they could rule out earlier contamination from an earlier partner or earlier event.

Makes me wonder, but falls short of convincing me.  Is it proving HCV occult, or the presence of other similar virus; (or both, or all of the above)

" HCV peptides detected in sexual partners and unexposed controls had sequence similarities to proteins found in other common viruses, such as herpes simplex virus and human papilloma virus.

I'm not sure if I am understanding the studies like somebody would w/ some science background.  That ain't me.....  : )

willy
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