Intestinal Reproduction of HCV : Questions??? TnHepGuy/all

[DoubleDose]

Noting the article linked recently by TnHepGuy regarding HCV replication in the small intestine, and the comment that the HCV particles seemed to be distinctly different than liver generated virus particles in the same patient, my questions are as follows:

1:  Are we beginning to see data that supports the controversial 'extra-hepatic' replication (and hence possible extra-hepatic transmission) of HCV???

2:  Could other people potentially acquire HCV in a "gastro-intestinal" form, rather than blood/liver????  Would they test Anti-HCV positive on serum HCV testing????

3:  Could mucosal (oral/ kissing/ sexual) contact allow HCV virions to travel to the gut, intestines, etc. to begin a reproductive process???

4:  Has anyone on the forum seen "HCV-like symproms" in family members, even though they test 'negative' on anti-HCV tests??
Symptoms like irritable bowel, chronic indigestion, stomach ache, loose stools, etc.... or other symptoms associated with extra-hepatic problems...like fatigue, memory decrease, dry eye syndrome, etc. ?????

5:  I wonder if there are any studies on previous HCV carriers who achieved SVR with treatment, and whose family members became anti-hcv positive at a LATER date...with no obvious risk factors??????  I have read studies of Japanese spouses becoming HCV-positive from their partners, only after many years of marriage.....something like 16% of spouses I believe!  Could this be from HCV transmission through other organs that in turn took many years to show up in the bloodstream??????  

Sorry for the 'off-track' concerns!

[LvdByGod]

HEY INTERESTING! DO YOU HAVE THE ORIGINAL ARTICLE POSTED BY TNHEPGUY? OR CAN YOU DIRECT ME TO THE POST THIS WAS REPORTED IN...I HAVEN'T BEEN AROUND THAT MUCH...THANKS

[Amerabrit]

You raise some interesting questions..  My husband tested negative and has shown no symptons whatsoever?  I believe my infection was caught in the acute phase so we both test very early on into the virus' life (within my blood stream anyway).  Lately, though I have been thinking about asking him to get tested once again?
I hope you're feeling well and in good spirits.

[TnHepGuy_]

You certainly do raise some good thoughts and questions.


My thoughts on what you have mentioned:

<i>1: Are we beginning to see data that supports the controversial 'extra-hepatic' replication (and hence possible extra-hepatic transmission) of HCV???</i>

This study theoretically points to replication within the small intestine. Whether or not that means anything in realtion to treating differently I would doubt, though. Eradication via tx is just that - there are no 'reservoirs' where the virus sits and waits for the right opportunity to rebound. I believe the authors in this study use the word 'reservoir' meaning a place in the body realted to replication - not a place where it hides out, untouched by the medications.

As far as 'extra-hepatic transmission' - I assume you are alluding to the possibility of external transmission. I guess my first question would be - is the HCV RNA that exists within these particles able to replicate on it's own as a 'separate' quasispecies of RNA? If so, that would point to the possibility of having multiple quasispecies within the body concurrently. Secondly, is it possible for these hybrid LVP's to exist anywhere but within the intestine? If the LVP quasispecies can exist only within the intestine, external transmission would seem highly improbable.

<i>2: Could other people potentially acquire HCV in a "gastro-intestinal" form, rather than blood/liver???? Would they test Anti-HCV positive on serum HCV testing????</i>

This also point to whether or not the LVP's have the ability to replicate anywhere beyond the intestine. If so, new qualitative testing might need to be developed.

<i>3: Could mucosal (oral/ kissing/ sexual) contact allow HCV virions to travel to the gut, intestines, etc. to begin a reproductive process???</i>

The virus would have to have the ability to survive the extreme acidic pH of the stomach to get to the intestine.

<i>4: Has anyone on the forum seen "HCV-like symproms" in family members, even though they test 'negative' on anti-HCV tests??
Symptoms like irritable bowel, chronic indigestion, stomach ache, loose stools, etc.... or other symptoms associated with extra-hepatic problems...like fatigue, memory decrease, dry eye syndrome, etc. ?????</i>

Speaking purely about my situation, my wife has not had any of these symptoms. I, on the other hand, have touched on all of those bases.

<i>5: I wonder if there are any studies on previous HCV carriers who achieved SVR with treatment, and whose family members became anti-hcv positive at a LATER date...with no obvious risk factors?????? I have read studies of Japanese spouses becoming HCV-positive from their partners, only after many years of marriage.....something like 16% of spouses I believe! Could this be from HCV transmission through other organs that in turn took many years to show up in the bloodstream??????</i>

Based upon the over 15 years history of interferon-related SVR patients - not to mention many more years of spontaneous clearance patients - who have achieved SVR and remained so for the long-term, I find it hard to believe that there is any kind of 'reservoir' of virus in hiding - holding back until the perfect opportunistic moment.

I'm not familiar with the Japanese studies you mentioned, but my thought would be to first look at the overall percentage of explained versus unexplained cases of Hep C that exist and apply those figures/data to see how many of the 16% unexplained in their study might actually be have occured via the more 'traditional' routes of transmission. Also, it might turn out to be that the 16% figure from a small study is actually statistically insignificant when put next to the overall percentage of unexplained cases.


TnHepGuy

[TnHepGuy_]

Here's the article:

<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15302945">Expression of hepatitis C virus proteins in epithelial intestinal cells in vivo</a>


TnHepGuy

[Sam Hall]

Forget not occult hcv.
SH

[DoubleDose]

Also note the above link listed today (by TnHepGuy) regarding the production of HCV specific interferon-gamma substances in blood mononuclear cells, EVEN THOUGH the subjects were negative on HCV antibody testing.  They noted that the inf-gamma responses were initiated by and MAINTAINED by possible sub-clinical HCV infection.....and implied that this inf-gamma response either thwarted or is still thwarting attempts by the HCV virus to establish itself.  My read on this is that it raises more questions than it answers!!!!  Why is the inf-gamma response ONGOING????  What is the state of HCV virus in these individuals (does it exist in their system, did it exist only in the past, or did it only ATTEMPT to attack their system?????

This provides MORE fodder for concern over potential extra-serum/extra/hepatic HCV infection, IF it turns out that low level HCV virions may be attempting to establish replication in the lymphatic system, mononuclear cells, or other organs.....

What do you think about this?

Yes it could provide hope for a vaccine, as they state, but could also merely mean that there are other ongoing immune response battles being staged in the HCV-neg. individuals being investigated.  

You wonder how many OTHER contacts with HCV infected individuals might also have this ongoing inf-gamma response in their systems.  This may be the 'unseen step' in potential infection or ongoing attempted infection within partners/family members of HCV positive individuals.  

Other thoughts??????

[bajawoman]

Interesting Thread from 2004  Any Comments????