What Do You Think About This Scary Study?

[JennyPenny]

Study: Patients With Resolved Hepatitis C Likely Still Contagious


Patients with chronic hepatitis C that has been resolved through therapy or immune response may still be able to infect others with the virus. That finding is from a new study in the May issue of Hepatology, a journal published by John Wiley & Sons on behalf of the American Association for the Study of Liver Diseases (AASLD). The article is also available online at Wiley Interscience (www.interscience.wiley.com).



About 170 million people worldwide are infected with hepatitis C virus, which can progress to chronic hepatitis, cirrhosis and even liver cancer. In some individuals, the infection seems to resolve, either spontaneously from the efforts of the immune system, or after treatment with interferon and ribavirin.



Patients who achieve a sustained viral response show no clinical or biochemical evidence of liver disease and standard tests can no longer detect the virus in their blood. However, more sensitive research tests are finding that such patients often still have miniscule amounts of the virus in their bodies. No one knows if these trace remainders are infectious.



Researchers led by Tomasz I. Michalak of Memorial University of Newfoundland, Canada examined this question using a system that allows for propagation of HCV in human T cells in vitro.



They began with nine patients with HCV who had achieved a sustained viral response that persisted for at least two years after treatment. HCV RNA was detectable in their blood only with the more sensitive tests.



The researchers set up twelve cultures of lymphoid cells from healthy donors, and exposed them to plasma or to supernatants of cultured circulating lymphoid cells from the HCV patients. Eleven of the cell cultures became HCV RNA positive. Furthermore, HCV from three of the nine patients was able to establish active HCV replication in the cultures.



“These findings provide in vitro evidence that trace quantities of HCV persisting in the circulation for a long time after therapeutically induced resolution of CHC can remain infectious,” the authors report.



Interestingly, HCV replication in the T cells was prevented after neutralization of the virus, and by treatment with interferon.



This study is the first to investigate the infectivity of HCV traces that remain when the infection is occult. It agrees with previous animal studies of the same question.  



“Our present findings reveal that HCV circulating in some individuals with resolved hepatitis C is capable of inducing productive infection in vitro at doses of 20 to 50 copies,” the authors conclude. “This can be interpreted as a strong indication of potential virus infectivity in vivo.”



Article: “Hepatitis C Virus Persisting at Low Levels after Clinically Apparent Sustained Virological Reponse to Antiviral Therapy Retains Its Infectivity in Vitro.” MacParland, Sonya A.; Pham, Tram N.Q.; Guy, Clifford S.; Michalak, Tomasz I. Hepatology; May 2009.

[nygirl7]

I've never really understood occult virus so I still don't understand how you can pass on something you no longer have but if the idea is that the interferon trains our immune systems to keep fighting any virus that might be left down to undetectible levels and it's not really GONE I still can't understand how someone could infect somebody else...unless they weren't at undetectible levels of "1" and it's that "1" that does it.

I've never heard of anyone who is SVR infecting anyone else before but all of this type stuff is WAY over my head anyway.  I'm not too worried about it myself as I'm not going to be IVDu'ing with anybody and I think that's the only way you could get pass it on anyway.

[JennyPenny]

I'm with you, nygirl. If I were undetected I wouldn't worry about it either. I also have never heard of anyone infecting someone else when they are SVR (which I consider cured). I think that maybe there may be a very very small amount of virus left in some SVR people....not enough to be infective, or counted in the bloodstream,  unless something happened that drove their immune systems so low the virus was able to overcome them.

[Willy50]

What do I think?  I hate to see it but it exists and we may not be able to deny it's existence.  We will have to be very careful of the way that we..... laymen....both interpret or attempt to re-communicate this evidence.  I think that we will be far more likely to come to a possibly false conclusion of the ramifications of this study than a virolgist.

I think one question that it poses if to how communicable the virus is post SVR.  I don't think it attempts to convey an answer to us and so I hope that we don't "fly off the handle" at this and can continue for the present time to obsess about the swine flu.  ; )

Many of us will be able to do what we have always done; maintain a safe and normal lifestyle without fear of transmission.  Might it be unsafe to share a needle with a past HCV positive but currently SVR person?  It appears that we might want to re-think that.  : )  I think normal day to day situations might remain unchanged.

best,
Willy

[apache1]

Hey JennyPenny

Could you please post a link to this study.
Went to
www.interscience.wiley.com
as in your first post and could not find it.

apache

[Rockerforlife]

I think to able to infect someone after one aquires SVR .you would have to injesct a full syringe of blood into the other person to catch it....if the virus is occult and is in muniscle amounts...i think it would be very hard to transmit.....like nygirl says....you would proberly have to on a 2 week shooting gallery bindge of partying to get it...im happy if i get SVR...i dont care waht they say...if my damage is stopped ....i doubt ill be spreading the C

[newleaf09]

I think "in vitro" is the key to understanding this.  They can make it infectious in a test tube.  Not the same thing as a human system.

I asked my doctor (an HCV researcher) about the virus re-activating about a month ago.  He said: The genome (the genetic material) of the virus remains in the liver.  It is unable to replicate (reproduce) because the treatment left behind a much stronger immune system (interferon induces killer T cell production).

IF you were to suppress your immune system (say with meds for one of the autoimmune diseases like lupus or rheumatoid arthritis or immunosuppressants for a transplant) it would be possible for the virus genome to begin replicating again.  I saw a study that suggested cured HCV patients wait at least 6 months before using such drugs.  I think I will just avoid everything like that until I am in dire need and hopefully by then they will have the whole business better figured out (kinder HCV treatment, more specifically targeted immunosuppressants).

I think we all know to exclude our livers from donor organs we may give some day.  I don't intend to worry about it all.  I've already changed my life this much and don't think I'll have much trouble refusing unneccessary prescriptions in the future.  It would be a good idea to mention past HCV infection to your other doctors so, hopefully, they will not prescribe immunosuppressive drugs to you for cassual reasons.

[mikesimon]

You wrote: "IF you were to suppress your immune system (say with meds for one of the autoimmune diseases like lupus or rheumatoid arthritis or immunosuppressants for a transplant) it would be possible for the virus genome to begin replicating again."

I don't necessarily disagree that it might be possible but I am not sure enough to say that it is possible either. I am immunosuppressed and have been since I achieved SVR in 2004. I test monthly with Heptimax and I am always undetectable. At one point in 2006 my anti-rejection dose was increased significantly for several months and there was no detectable virus then or since then.
I have really studied this subject and I don't know the answer. I have citations that suggest that the virus can become detectable with extreme imnunosuppression and other articles that say differently.
Mike

[apache1]

Without being able to read the whole study, many questioned persist for me.

===========================================================
"They began with nine patients with HCV who had achieved a sustained viral response that persisted for at least two years after treatment. HCV RNA was detectable in their blood only with the more sensitive tests. "

'Researchers led by Tomasz I. Michalak of Memorial University of Newfoundland, Canada examined this question using a system that allows for
'propagation'  
of HCV in human T cells in vitro."

===========================================================
What more sensitive tests where done ?
What strand of RNA did they detect, + or - ? was it a full strand ? or crippled ?

Sounds like this research team put what ever remnant they found on life support in the lab till they got it to bloom again.


First many researches call any remnant mutated disabled crippled partial strand of something resembling hcv 'occult virus'.
I have been told this is not entirely correct labeling, since it confuses 'hBv' occult virus that is a very real occult virus just at low levels, and HBV does and can come back full force infection, and is transmisable.
This has never been the case with SVR HCV occult or otherwise, in any study I have ever read. SVR for HCV is durable. Not so for occult HBV.
If anyone has a study to show occult hcv was transmitted or came back in a new infection I would like to see it.

Also, many of us have all types of other virus remnants in our systems from previous infections...mumps, chicken pox, etc is this occult virus ?.... These other remnants do not cause reinfection or are transmissible to others in a real world situation. Unlike a petri dish lab experiment.

Many right on this forum are SVR and on current immune therapy for their tp liver or other organs.
Some even went on tx after they were on immune suppressants and got SVR. Have never seen or heard of a documented case of virus breakthrough or reinfection for any of these immune suppressed SVR people. I have read studies verifying this also.

jmo
apache

[portann]

Dear Jenny,

Thanks for posting this article. Very interesting and disquieting topic.

I found a similar thread from an earlier Polish study, to which Mike replied with various other studies:

http://www.medhelp.org/posts/Hepatitis-C/SVR-personsPersistence-of-HCV-After-Successful-Treatment-of-Chronic-Hepatitis-C-Is-HCV-Infection-for-Life---/show/98641

Forgive me if the link is not apropos today. I thought it was a clever and cute move on Mike's part but I confess I skipped the reading requirement.

Does this study mean I have to take extra precautions not to mingle my liver with my husband's during sex? :)

[oneatenuff]

Interesting.... ("strong indication")  though I've never understood fully the "occult", either.  I've understood what I thought was the basic worry  (that it's been detected in certain body tissues such as lymph and that what we though was "gone"  isn't really gone.)   My doc at Duke said that for practical purposes there's no need to worry about occult HCV and gave the explanation as to why, but I can't remember why - I recall not understanding it fully when he was explaining it then, which was a few years ago.  Point being - there is "occult", it's very confusing, but from his standpoint at that time it was totally not worth any consideration with respect to treatment  (the worth of it - even though there is the "occult HCV" that is being researched and being found)  ..... or something like that - lol..  

There's no telling what's going to be learned about HCV in the next 10-20 years  (hopefully enough in the next 5 years that will speed things along to a vaccine, even.)    

Interesting read.  Thanks for posting it.  

[Rockerforlife]

if i get SVR at 12 and 6 months EOT....thats all that really matters...the rest is hog wash

[jmjm530]

I echo other comments on being careful to draw real world conclusions from an in vitro study. Same on Mike's thoughts on the role of the immune system plays in SVRs. The fact that we therefore don't see more relapses because of suppressed immune systems seems to suggest that whatever remnants may be leftover are not viable enough for transmission.

-- Jim

[Bill1954]

This may just be an issue involving typos, but I was about to mention the same thing; that in vitro results are much different than in vivo. However, they must feel this evidence is compelling enough to directly quote at the end of their summation “This can be interpreted as a strong indication of potential virus infectivity in vivo.” Pham has been involved with these phenomena for quite a while; he’s listed as coauthor in this work.

I’d personally like to see more studies; although an in vivo study is going to be difficult to perform given the obvious ethical restraints in place. Possibly with chimp models? Very interesting. For those so inclined, TnHepGuy_ and others have assembled a page dedicated to the investigation of occult/persistent HCV:

http://www.medhelp.org/health_pages/Hepatitis/Occult-Hepatitis-C/show/54?cid=64

Bill

[jmjm530]

last sentence should have read: The fact that we therefore don't see more relapses because of suppressed immune systems seems to suggest that whatever remnants may be leftover are not viable enough for relapse and/or transmission.

-- Jim

[newleaf09]

I'm not a researcher so could not make claims of veracity for ANY of the studies.  I think we've all read some that are obviously bad science but managed to get published anyway.  I took graduate statistics and found it depressing that you can make your point by choosing specific statistical analyses that push the proof in a specific direction.  Just repeating what my doctor told me.

Mike, thanks for encouraging us with your personal experience with immunosuppression.

Apache, you are making me wonder about all virusses leaving remnants, not just antibodies.  Chicken pox does cause shingles in older people.

[JennyPenny]

last sentence should have read: The fact that we therefore don't see more relapses because of suppressed immune systems seems to suggest that whatever remnants may be leftover are not viable enough for relapse and/or transmission.
-------------------------------
This is what I believe also after thinking about it for a while. It's an interesting thing to discuss, but none of us has seen this type of thing happening in the real world.

[JennyPenny]

Here you go: http://www3.interscience.wiley.com/journal/106570044/home

[jmjm530]

One thing that came into my mind after reading was all the magical things scientists can do in the lab with let's say infertile couples who cannot otherwise reproduce in the real world, but if you try hard enough you can produce something in a test tube. The reality is that CHC s not very efficiently transmitted in the real world. Needle stick accidents around 3% transmission and sexual transmission either rare or non-existent in monagamous hetero couples depending on who you talk to. And that's with a viral count usually in the millions or tens of millions, not the so called occult which is below the detection range.

[Rockerforlife]

To contract HVC from  SVR patient,you would have to a vampire and drink a gallon of their blood

[desrt]

"...HCV RNA was detectable in their blood only with the more sensitive tests..."

That requires some clarification. What tests showed "detectable" and what did they show.

[willing]

This paper got a discussed a bit in a thread portann started about a month ago

http://www.medhelp.org/posts/Hepatitis-C/Cell-in-top-100-of-past-century/show/918781

I was surprised it didn't generate much discussion since it seemed a pretty interesting find, but assumed most people were just bored with occult hcv. The detection issues are not the news here.  The tests are standard RT-PCRs with a sensitivity of 2vge/ml, comparable to the NGI superquant, but with an important distinction: they examine extract from whole cells (lymphocytes and hepatocytes) whereas commercial tests only consider serum. In addition to detecting the coding (+) and replicative intermediate (-) RNA strands, they detected viral proteins via immuno-staining.

None of this is new. What is new is the demonstration that  residual, post-SVR virus is capable of infecting other cells, ie the has-been virus, though only a shadow of its former itself,  can still manage the basics. There are qualifications : not all patients were  able to yield infective virus and infectivity was demonstrated in  an in-vitro setting where the recipient lymphocytes were artificially stimulated/manipulated.

Whether in-vivo infectivity can be shown will be revealed in the next installment. I assume the Pham/Michalak lab is presently  working on those experiments. As noted in the above thread however, in some sense that experiment has been going on for a while :

"On a different tack, it seems some evidence should already be available, anecdotally, in human  organ-donation data.  How many cases of HCV transmission from SVR-donated organs have been recorded? "

[Rockerforlife]

AMAZING QUESTION

How many cases of HCV transmission from SVR-donated organs have been recorded? "

[JennyPenny]

That's an interesting question. But I thought that HCV organ donations are only given to people who are HCV positive. I don't think there is too much to worry about here. And it seems that you all agree. I was wondering if the SVR is a cure faction would feel the same as the SVR is just remission people would think differently.

Oh, I just got a note from someone named Ugly (very appropriate I might add) who called me a fear mongering internet babble something or other. Had my laugh for the day.

Have a great night everyone.

[apache1]

Thanks for the link Jenny

This article did mention much collected data that did not directly apply to this particular study of 9 patients.
Such as PBMC and liver vl.  Imo no reason to mention in this article other test methods that were NOT used on these 9 test subjects... seems misleading to me, maybe purposely ?

After reading this study in full, my laymen conclusion is, this study used patients with less than satisfactory viral load SVR testing. The tests used for the
9 "clinically apparent SVR" study patients, only went down to
***500 iu/ml.****

Then the study lab used very sensitive tests of <2 or <10 for those 9 study patients, and came up with blood serum vl loads of <40-400 .
These patients were now labeled as having occult hcv with vl of <40-400.


=============================================================
Nine patients who achieved SVR after completion of IFN or IFN/ribavirin therapy, as defined by repeated serum HCV RNA negativity by the Roche Amplicor HCV version 2.0 assay

****(sensitivity, 500 IU/mL or 1000 vge/mL****

; Roche Molecular Diagnostics, Pleasanton, CA) and normal liver function tests assessed at 6- to 12-month intervals, were investigated in this study (Table 1). All patients were anti-HCV antibody-positive by enzyme immunoassay (Abbott Diagnostics, Mississauga, Canada). The follow-up period after SVR ranged from 24 to 72 months. All nine individuals were found to carry HCV RNA at the time of this study when total RNA isolated from 500 L of serum was assayed by highly sensitive RT-PCR/NAH (sensitivity of 10 vge/mL or 2 IU/mL) that was previously established.[2] The estimated HCV

***RNA loads in the patients' sera ranged from <40 to 400 vge/mL***

==============================================================


Now we as patients have better vl tests available to us here in the USA.
Quest has the Heptimax good to <5
LabCorp has the NGI <2

So if we all get the sensitive tests done at 6 month post eot, then this complete study, regardless of its accuracy,  is null and void for any one that shows negative on sensitive commercially available viral load blood tests.

apache