Is anyone concerned about family transmission issues? or occult transmission?

[DoubleDose]

This may be an 'off the wall' question for many on the forum, and yes I know that some of you have heard similar questions from me in the past, but I am more curious than ever if anyone is seeing any familiar symptoms in close relations, family members, intimate partners, etc.  I am addressing those who have lived with HCV in the same household with other family members for ten or more years.  

I am aware that there is a research study being done by a prominent hepatologist to explore these issues.  They will be testing tissues, fluids, and other cell structures in HCV negative family members, to determine if there is any indication of some other form of infection.  I have been concerned for more than a few years that there may be another 'mode' of infection that may take place through casual, or intimate contact, and which does not produce the typical blood/liver infection nor does it produce a positive result on HCV blood antibody testing.

Curious symptoms might include things like:

*  Unexplained dry eye, and salivary irritations.
*  Chronic fatigue and unrefreshed sleep, becoming worse over    the years.
*  Abnormal forgetfulness and noticable short term memory problems.
*  Arthritic pains that did not exist in the past, in areas like neck, shoulders, hips, and ribs.
*  A reddish flat rash that occurs on the face around the eyes, and comes and goes for no reason.
*  A chronic sort of allergic state, with inflamed sinuses and throat, and daily throat clearing, year round.
*  New gastric and bowel issues.


Comments Appreciated!

DoubleDose

[cuteus]

looks like the thread is now buried underneath the ruble of newer threads, but to those still peeking, the trip to Boston did not pan out. A very dear AnCom (animal companion) decided it was time to cross the Rainbow bridge, and it was not a good weekend to think of HCV.  
If any conferences occur in the tri state area of NY/NJ/Ct I am game to being a pest, but I want company!  Seriously, I will check for anything worth it in NYC, there has to be something!

[jmjm530]

Readings corresponded to the doctors I saw.

Went like this:

First reading, three years prior to tx by hepo 1's pathologist (stage 3). Ended up not treating with him; Second read, one year prior to tx by hepo 2 who I treated with for one week only(stage 3); Third read around 7 weeks into treatment by hepo 3's pathologist who I also didn't treat with but used as a one-time consult(stage 2); Fourth read somewhere mid-way into tx by  my treating doctors pathologist to reconcile all the other reads :) call him hepo 4 (stage 2.5); and fifth reading later on in tx as part of my Fibro*scan process (Slightly south of stage 3). So I guess that makes it five readings from the same slide.

But like I said, different readings between stage 2 to 3 isn't really that strange considering it has to do with the "maturity" of bridging taking place and how the pathologist views that.  

The Fibro*scan itself showed me somewhere between stage 2 and 3 which was very reassuing since it was current as opposed to three years old. Because of the anti-fibrotic nature of tx, it's c possible that I would have scanned higher before tx as opposed to during tx. Still, I "concluded" that I was a stage 2.5, as did the scan doc.  I had another scan four months post tx and it showed me very close to stage 2 which was very reassuring. I wanted to come back in another year but he basically said that I was "through", "cured" and wished me well :) He also indicated that in the next couple of years these machines hopefully will be all around the country.

Part of my angst was that the studies I was looking at lumped stage 3 and stage 4 together in terms of extended tx. Later, the consensus seemed to be that only stage 4 was a negative predictive factor.

It's possible you will also get different reads but if your first was stage 1, I doubt if any of them will be higher than stage 2, which is not a bad place to be sitting at this point in time. Also, if you're as compulsive as me, consider a scan at one of the 3-4 trial centers, assuming the trials are still going on. Dr. S in Miami also has a scan machine but don't believe he's in the trial. Also heard another doc in CA has the machine but not sure who. I'm sure an email to the manufacturer's of the machine will let you know who has it.

All the best.

-- Jim

[willing]

I'm not sure I buy the can't-be-bothered-to-refute argument. If  Pham's observations are bogus, letting them stand unchallenged for 3 years, as the citations to his work pile-up, seems very unlikely. Researchers get excited about much more minor issues, and refutation wouldn't be difficult, eg if the LB9 authors had used the Pham/Radkowski methods in addition the commercial versant tma
(Cuteus : it's Monday, Exhibit Hall C, Hynes Convention center, starting at 8:00 in case you decide to go. Set up as a poster session, so one of the authors should be by the poster most of the day).

4 readings - wow! I'm awed by such thoroughness, and you even got one of them to talk to you (not easy, I agree). For my first two bx's I simply took the word of whoever they were assigned to but since the last result is unexpected (why down to stage 1?, are you *really sure*?) and because I'm  betting rather heavily on it (by delaying  re-tx)I'd like to get an estimate of  observer variance (you say "mild" I say "moderate"..). I'm doubt I can match 4, but thanks for the inspiration!

[nitramog]

alot of thes simtoms are normal non hep simptoms, are systems are weakend, the same food can bother peoples stomecs, treas in the yard, one person wea love is sick its hard to sleap,   esey to have some depreshion i think?  some times a cloud is just a cloud ?  i hope!  i hae wonderd the same question

[jmjm530]

Second to last paragraph should more accuratly read in part...

"While a stage variance seems like a lot, the difference between 2 and 3 has a lot to do with how an individual pathologist views the extent of the bridging."

In fact, two of the reports (a 2 and a 3) sounded almost identical but each pathologist made their own judgement call. By the book, you're not supposed to get a Metavir 2.5 as the book uses just whole numbers. Still, the pathologist (the one who let me look into the microscope) felt that 2.5 more accurately defined my stage. When pressed for a whole number, said it would be a 2. Why the others decided on a 3 I'll never know because neither of the pathologists were very forthcoming when questioned and that's an understatment :)

[jmjm530]

I understand what you're saying but in order to unequivocably disprove these newer studies, wouldn't the clinicians mentioned have to in a sense run more or less duplicate test studies? This may indeed happen in the future, but it's understandable why someone wouldn't want to invest a lot of time to disprove something that they and many of their collegues don't believe in. Most of these fellows are putting their energies into the newer class of protease inhibitors.

What about the study DD cited (LB9) where "They looked at serum samples, liver samples, and PBMC samples, and found NO relapses, and only a couple of cases where the liver or PBMC's were found to be HCV+. The rest of the study group were negative in all compartments studied." It might be interesting to look at the complete study as opposed to the abstract and see if any references are made to the studies where viral activity was found.

You're certainly more up to date on this than I am. Why don't you email some of these Clinicians who include pretty much all or most of the "big" names, and see if they will detail their reasoning more. I've had some luck in this regard contacting researchers on other areas of interest to me.

You might even mention Mike Simon's case to them, but unless you really quiz his doctors regarding methodology, etc, I'm not sure how they would be able to respond.

So how do you like them Vertex reports today? I know you think it's still a video game until the SVR data comes in, but within a year a ton of SVR data will be in.

BTW read a bit on your biopsy shopping. Be prepared for different reads. I had the same slide read 4 times and in terms of stage got a 3, 2, 2.5 and another 3. While a stage variance seems like a lot, the difference between 2 and 3 has a lot to do with how mature the bridging is.

One thoughful pathologist let me look at the microscope and I pretended nicely to know what I was looking at. In other words, at a certain point it becomes as much art as science. Still, if I remember correctly you also were staged around 2 or 3? And while you may get some variances, you can feel pretty confidant that you're not a 0 or probably a 1 and certainly not a 4. So in that sense, the biopsies are extremely helpful. The problem is when someone says they were a 3 and then they treated and now they're a 2. Maybe the fibrosis regressed, or maybe just more pathologist bias.

Be well,

-- Jim

[willing]

the trouble with the many clinicians who dismiss the occult/residual rna detection as sloppy/spurious bench work is that none has yet been willing/able to support this point of view in a peer-reviewed journal. Furthermore, a couple of the occult papers come out of the Mayo clinic, not known for sloppy work (see the tail of the 10/23 2006 Liver Meeting thread below for a list 41 of publications that have cited the original occult study).

If you accept the PCR data, this leaves the non-viable and co-existence theories. The non-viable theory is made suspect by the detection of - strand RNA,a side-effect of replication. IMHO the co-existence theory is the most plausible. I tend to see it analogous to the common stories of an inner-city park/neighborhhod reclaimed from a crack-dealer/prostitute  occupation. You haven't really eliminated the problem, but you've changed the equilibrium and the change is durable. Once you develop the right T cell response, it sticks.

In case you missed it, for direct evidence of how an UND <5 blood test can be obtained in the presence of HCV-infected liver tissue see Mike's comments in the 10/25 ITMN-191 thread

[jmjm530]

MR: He said that those reports are not universally accepted within the HCV research world, and that the test methodologies were being hotly contested by many, including some of his research colleagues. He said they believed their test methodologies were suspect and possibly prone to sampling cross contamination.
----------------------------------------------------
We may be seeing some of the same doctors because that is almost verbatim what one of my consulting hepatologists said :) He also used something like the phrase "questionable tests that were unreproducible using accepted and verified testing techniques". Another doctor questioned the significance of the findings as to whether or not the virus was fully capable of reproducing.

Of course, like you suggest, this doesn't mean occult and persistent virus doesn't exist -- and indeed it may turn out to be a very important issue down the road -- but until something more is put on the table, I'll be more than happy with my SVR. An interesting topic, though.

-- Jim

[mremeet]

My dr is a very experienced/respected hepatologist at a major research hospital and I actually posed this "occult infection" question to him (based on the referenced reports) prior to starting my treatment. He said that those reports are not universally accepted within the HCV research world, and that the test methodologies were being hotly contested by many, including some of his research colleagues. He said they believed their test methodologies were suspect and possibly prone to sampling cross contamination. The cross contamination might have explained the apparent presence of the virus where in actuality it may have been absent. The sensitivity and very high amplification used in the extremely sensitive tests involved apparently makes it easy to score false positives if you are not absolutely/rigorously/inscrutibly scientific in your method.

I also pressed him a bit on the whole concept of "cure" for SVR's, and he was very comfortable using the word "cure". He didn't use it lightly and said that based on his extensive exerience with SVR's that he really believed that the virus was permanently eradicated. And this guy by definition is your stereotypical conservative western doctor; again, he didn't use the word "cure" lightly.

Of course it was just his opinion, albeit a highly informed one. Who knows, maybe there really are occult "quasispecies" that somehow persist within the body at very low levels long after SVR-ing? But persist in an (apparently) benign way?? Anything's possible, but it would seem to me that if there truly are viable, reproducible, true blue HCV RNA floating around inside the bodies of nearly all of the thousands of SVR's out there (as these studies assert), I'd think you see a clear pattern of resurgence in those who later became immunocompromised (via AIDS, cancer, or other serious illnesses). Surely at this point, after many years of experience with 1000's and 1000's of SVR's (via drug induced and natural clearance), a decent sized subset of those folks have gotten very sick in an immunocompromised fashion (via an unrelated illness). I'd expect to see at least some kind of statistically significant uptick in relapse rates in this group. And if that were happening, I'd think it would be noticed, and reported on with some regularity (especially within the HIV/HCV coinfected and transplant/drug induced immunosuppressive groups).

These studies do state/suggest the "occult" HCV RNA found *is* viable and reproducible. Viable and reproducible to me means just that - viable and reproducible. And identifying what was found as "HCV" and not some different, mutant quasispecies, states pretty directly that it *is* HCV. And if it is HCV, by definition HCV opportunistically infects the liver on a large scale if the immune system is unable to eradicate/suppress it upon initial infection. And we certainly know that those who SVR via drug therapy, or whom clear naturally, can be reinfected. There is no immunity to HCV after clearance, reinfection can and does occur. So what seems confusing to me is that they call what was found "HCV RNA", and they say it's viable and reproducible, and yet there is no accounting for why so very few SVR's have historically been observed to relapse. And again especially in regard to the growing long observed body of both natural and drug induced SVR population, and especially within the previously mentioned immunocompromised subset within that group.

Just my $0.02, but until I see some more widely repeated and convincing evidence backing this theory up, I'll continue to pursue my SVR with a sense of comfort and confidence in what it will mean to my health if I manage to clear this damn thing.

[GoofyDad]

How come you folks are listing gastric/bowel issues in the  complaints dept? I mean, to my way of thinking they're a gift. Like playing the piano (or tuba), and painting velvet elvis pictures. Or maybe porcelain Elvises would be closer ....

[Kalio1]

I think you misunderstood what I meant. I meant "occult virus" in the vast majority of people is no more harmful than having had a childhood illness in the past.

I know the difference between antibodies and active virus.
I should have used a better analogy.
FOr instance, I had chicken pox pneumonia as an adult and it left behind marks on my lungs but they cause no harm to me, maybe that is a better analogy. You can see them, but that doesn't mean they are hurting me now.

I think to worry about things like this and waste time and energy on it is liken to worrying about a meteor hitting your house or lightening striking you, just not worth the energy.

[DoubleDose]

Kalio:
When you say 'finding the occult viruses of past childhood illnesses' I think you are confusing 'antibodies to viruses' with actual viruses from childhood.  The evidence of viruses from old infections is just the (harmless) antibodies to those prior infections, which often remain for life.....not living, replicating viruses.

With 'occult HCV' on the other hand, there is actual replicating virus present, just a lack of antibodies that would let us know that the virus is there.  What these researchers are looking for is actual replicating virus in various tissues and fluids.  They do not know what the possible ramifications of this sort of low level 'hidden virus' might be.  If it is happening, no one has yet determined that it is either harmless or harmful, yet.  That is what they are also going to be looking at.  

I personally feel that a study of this sort will be very enlightening, and will help us all either feel much easier about the possibility of casual transmission, OR...will cause greater concerns.  Whatever the outcome, I want to know the facts.  Good research will uncover them.  

Revenire:
Have you ever been concerned about these familial symptoms, or connected them to a potential HCV cause?  I was initially thrilled when my family tested negative for HCV, on multiple occasions....but then, seeing the ongoing symptoms, and hearing about studies like those mentioned above, I began to be much more skeptical, and concerned.  I am not jumping to conclusions, or being an unwarranted alarmist, but just reacting with suspiscion to my ongoing observations.  I would love to find that my fears are totally unfounded.  Remember, if this tissue related, localized infection does exist, it will probably be held in check just like an SVR, and will probably never become a full blown HCV blood infection, barring some immune system disaster.  But it would also probably never be detected on typical blood/antibody testing, since there never was a blood borne, or acute HCV infection to produce the antibodies in the blood.  This is why the study is looking at fluids and cell tissues...to see if the virus is there replicating, in isolation.
I am very curious about the findings.

DoubleDose

[mikesimon]

From Tram:
"On the other hand, virus persisting at very
low levels may provide a means for reactivation of infection
when the host

[Kalio1]

What I understand from the occult studies is even though they have found evidence of the virus, there is no manifestation of medical issues related to that. They aren't sick. They aren't experiencing any ongoing health damage.


The studies are hard to interpret. To me it seems that for most who achieve SVR and remain healthy being able to find evidence of occult virus is nothing more dangerous than being able to find "occult" virus of past childhood illnesses.

My question is if you were to develop some new dramatic illness, is it possible for that amount of "occult" virus to reactivate?

[can-do-man]

Married 27 years and wife is negative. My thoughts are her  chronic nagging keeps the HCV away. JMHO

[mikesimon]

I can see how that article would scare anyone but it must be viewed in the broader context of how SVRs do in general. It appears that aside from annecdotal evidence achieving SVR carries with it tremendous benefits notwithstanding the fact that with extremely sensitive detection tools some evidence of HCV can be seen. Liver disease progression is halted and the risk of HCC is drastically reduced in the vast majority of SVRs. I have not seen any evidence of transmission from an SVR either - at least not where it can be detected upon "gross" examination. What is going on deep down in the cellular goop is a matter of conjecture and a subject area ripe for study and investigation but, from an overall health perspective, SVR appears durable and its benefits durable and for most of us that's enough. Problems can and do occasionally arise when our immune system is tampered with but that shouldn't be an issue for the overwhelming majority of us here. I feel a whole lot better being an SVR even though I do have some issues resulting from my immunocompromised situation. But, my liver architecture is pretty good and one hell of a lot better than it would be had I not achieved serum clearance or SVR. In conclusion SVR is a great place to be for anyone infected with HCV and all the rest of this stuff is, for most SVRs, purely academic. Good luck. Mike

[GrandOak]

I too was concered about family transmission and found the answer for me was to simply have them tested to know for certain.  

In all cases, praise God, the tests all came back negative as I know it would have caused me great distress to think that I may have been responsible for their infection if any of them had come back positive.

[jmjm530]

Thanks for the information. As you know, some question the accuracy/validity of the new testing process itself in regards to at least persistent virus. Having a control would certainly go a long ways in addressing this problem. Willing, I believe, posted that AASLD study abstract # LB9 suggests that the absence of post SVR virus in all compartments studied including PBMCs and Liver tissue with the exception of just a few cases. Then, of course, other studies, using different amplification/centrifugal techniques suggest the virus is quite common in these same compartments.

Be well,

-- Jim

[DoubleDose]

I will get study details for you.  I have been in touch with the group running the study, but have not communicated directly with the chief doc yet.  I would like to learn more about the study parameters, and how far and wide they will be looking.  Also, to what extent they will biopsy and PCR test the various tissues and fluids, etc.  Although it would be nice to see test results also from households without anyone positive for HCV, as a sort of control group, I do not think that it will be necessary as a first step.  All they need to find in this study is evidence of active, and replicating HCV in the family members' fluids and tissues.  That alone will be a major revelation itself, if that is the outcome of the study.  Of course, I hope they find NOTHING of the sort.  But at this point, I would not place any bets on that happening.  I am more and more convinced that something may be happening, under the radar, as far as 'occult' transmission, and another, different 'mode' of infection.

Let's first see if they find the virus, then consider studying the general population, as a control.  Who knows, there might be some revelations in that study as well! I am just happy that they are finally exploring this issue scientifically, since it has been a real concern for me over the recent years.

I hope you are well.

DoubleDose

[GrandOak]

C28  . Married 27 years and wife is negative. My thoughts are her chronic nagging keeps the HCV away. JMHO

LOL, and you're hoping to make 28?  Your odds might be greatly enhanced if you keep here from reading this forum <G>

[Willy50]

I'm concerned of course, presumably anyone with HCV would be unless they strove to lead a hermits existence.

It's a good question but another equally good would be would be; how likely is it?

It might be useful to qualify the answer; if it were possible and likely in 100% of those that live with us..... then we should all get very nervous.  Of course....... IF that we true we would have already seen many many unexplained cases of HCV.

If the "what if" occult transmission scenario includes that the people never develop symptoms, antibodies, or HCV..... it just seems to be one more thing to worry about.  

When I think how long I have had the virus...and all the people that I have had various forms of contact with that I could have infected but that have not become infected even after decades I think that you can infer that the virus is not easily transmitted.  I believe epidemiologists have had the means of determining and proving this.  If it were very possible we would simply see a higher infection rate.  

I agree with you that science has shown that some HCV can remain even after one achieves SVR.  I would think this might be a more likely area to look for the virus regenerating itself.  So far however the stats on that suggest that less than 1% lose their SVR; even that might be due to the less sensitive PCR's available a few years back.

It may be true that it is scientifically possible.  It might also be true that what you are talking about occurs in a statistically insignificant number of people, otherwise it would have been detected.....and proven by now instead of being discussed as a theory.

Of course...all bets are off if there a scientific conspiracy of secrecy......  : )

A great question, and just my opinion.....

Best wishes,
Willy (whose kids also test clear of the virus)

[beamishboy]

mike posted a research article about occult & persistant viral presence after SVR...very scary...they found replicating virus in 80%+  patients (mike correct me if i'm wrong) and basically conceded that virus remains within us after successful TRX !!.....their methodology is beyond my comprehension/education...basically cultured samples and produced measurable population levels...bottomline? : it lurks,lingers and can raise it's uglyhead given opportunity ...... Sooo,yes ..i am concerned about occult virus...far less so with transmission

[Kalio1]

* Unexplained dry eye, and salivary irritations.
* Chronic fatigue and unrefreshed sleep, becoming worse over the years.
* Abnormal forgetfulness and noticable short term memory problems.
* Arthritic pains that did not exist in the past, in areas like neck, shoulders, hips, and ribs.
* A reddish flat rash that occurs on the face around the eyes, and comes and goes for no reason.
* A chronic sort of allergic state, with inflamed sinuses and throat, and daily throat clearing, year round.
* New gastric and bowel issues.

These complaints could be attributed to an enormous variety of causes.

If your family is experiencing these symptoms, I'd have your houe checked for mold. Homes with a mold problem can cause these symptoms. To attribute them to HCV when not one family member tests positive for HCV seems highly unlikely.

Household mold on the other hand could be a possibility. There are progessional inspectors who can ascertain if your home is contaminated with molds.

[Eyedeas]

The stress of living with a family member with a chronic illness is enough to cause most of these symptoms, not to mention normal allergies, and environmental conditions.

HCV sucks big time, and I think there's a tendency to try and blame it for everything that happpens to us and ours.  There are a lot of other health issues facing families.  

Kim