Full-length article re: post-SVR study of occult/persistent in liver

[TnHepGuy_]

For those with an interest, here's the full article of the recent study by Castillo, et al:

<a href="http://www.natap.org/2006/HCV/120606_11.htm">Hepatitis C Virus Replicates in the Liver of Patients Who Have a Sustained Response to Antiviral Treatment</a>


From the paper:

"<i>We also found that the loads of positive- and negative-strand HCV RNA in our patients were significantly higher in PBMC samples than in liver biopsy samples, which suggests that the HCV strain detected in our sustained responders replicates more efficiently in PBMCs than in livers.</i>"

"<i>...15 patients had continued liver necroinflammation, and 1 patient had liver fibrosis; however, there was an overall improvement in histological damage. So, it is difficult to know whether persistence of HCV infection and replication has a clinical relevance until more data become available.</i>"

"<i>In summary, HCV persists and replicates in the livers and PBMCs of a high percentage of patients who received antiviral treatment for years after normalization of liver enzyme levels and clearance of serum HCV RNA. Although it may be suspected that the risk of HCV reactivation is smaller than the risk of hepatitis B virus reactivation, persistence of HCV in these patients should be taken into account under special circumstances (e.g., immunosuppression or chemotherapy).</i>"


TnHepGuy

[sfbaygirl]

I asked about jumping right back in like you did. I would think that would make a difference. He hadn't read the whole thing yet. He thinks it has some important info though. Especially for those who wait and see, don't extend and those with high fibrosis and re treat. I am interested, as I am sure you are, about this study. I wonder if the lengths of tx are discussed for retreating? I don't know if it is non responders or relapsers, this would sure make a difference. I guess too many questions to speculate now. One of us has to go to the library. Hahahhhaa Maybe next week we can shuffle on down there...LOL

[Kalio1]

It's too pricey for me, but you can get it at the library.

I'd like to read it too because I can't tell from what HR posted if they were nonresponders, relapsers or what. I did read the HALTC info (they have a web site) and it appears they treated for 24 weeks (?)if clear by 12? Who knows!

[sfbaygirl]

Does anyone have access to this article we have been talking about. I went online and they want 1100. a year for a subscription! That's outta my budget.

[sfbaygirl]

One of the things I took away from my converstation re this article was that it is better to extend than to retreat. The chances of SVR  with re treating go down, to people with low fibrosis to 30% and to those that retreat with high fibrosis to 9%. That is a grim statistic. All those thinking about extending should take note. I think what HR is saying is that with this huge study and great chance of lowering svr chances for those with high fibrosis when retreating, we need to consider this in our tx options. HR, please correct me if I am wrong.

[GoofyDad]

Great news on the Hep. Now we'll try to wean you off the margaritas and bad porn. Or maybe 'wait and watch' the  appropriate course.....(or is that sip and watch)?

[cuteus]

I have never regretted treating at stage one, grade two.  I did have the option to wait a bit, but aging was not waiting and no one could tell me how fast MY damage was going to progress.  It made sense to treat while liver was mildly damaged, I was relatively young, had good insurance (thank G for that!), and a secure job.  Many factors to consider.  No one should wait based only on level of damage.
I believe the liverdisease.com site also suggests treating while damage is mild.

In light of all my fellow hep c relatives that are still struggling to decrease the freaking thing from their blood, I consider myself extremely lucky, and willing to live with whatever diminished, stunted remnants might be left in my PBMCs.  20 patients is not a great sample, and even there, not everyone had negative strands.  It is never 100% anything.  
I also consider myself cured from hepatitis, whether there are traces of whatever in the liver, I will need to see prove that it is affecting my liver or other tissue negatively before worrying about it.

[Skepsis]

I am definitely not the "watch and wait" type of HCV-veterans, having received 5 therapies, the last two being completed full time PEG-Combos (classified as "partial responder"/relapser).
I guess about half of us (or more, a rapidly increasing population anyway) are non-responders. This is the most significant portion of HCV patients seeing the hepatologists, including the most interested and in HCV-issues educated patients  - the most readers here on this forum are by now non-responders, I guess. Our dilemma is not "to treat or not to treat", but what can we do to prevent or postpone liver fibrosis until we get some cure.

It is a purist attitude, that can easily be hurt by perpectives having to live with persistent virus remnants. This is a psychological pitfall of our half digested school education, the same one which turned out to be very harmful for provoking allergies:  excessive disinfecting behavior (or EDB :-).

It is a more mature attitude to accept our live is worth living in symbiosis with a virulent virus population.  

My CONCLUSIONS:

1. Achieving SVR is a worthwhile aim for all HCV-infected people, despite of limitations.

2. There is a double motivation for having our liver in good shape: beside increasing our general living capacity the chance for a cure is depending on it directly!  

3. Therapy is a good opportunity for treatment-naive people.

4. For Non-Responders should any other measures with a potential halting fibrosis be of interest.

I personally drink now more coffee and green tee, have recently changed my blood-pressure medication to losartan (irbesartan could be another option), because these all have potential antifibrotic capacity attributed.

[GoofyDad]

Still makes sense to me that a stage 1 or 2 has the option of waiting it out. Lots depends on rate of progression, lifestyle and what they're waiting for. I don't think anyone has advocated knowingly waiting for cirrhosis before treating. Interferon would not be my recreational drug of choice.

[Eisbein]

Haha, I used to encourage tx till blue in the face. Gotten myself into arguments or got ignored. The "Interferon is poison, and stage 1 and 2 can wait" crowd outnumbered Cuteus and myself almost all the time.
Maybe some 'watch and wait' members see your post and listen up.

Ina

[Eisbein]

I saw my hematologist/medical/oncologist about unrelated hepc stuff yesterday.
He knows I am SVR. Thought I quiz him a little.
Do you think I have remnant virus in liver, PBMC, lymph tissue, etc....of course you do, hope you weren't told otherwise.

How come you know, you are not specializing in viral hepatitis...I treat liver cancer, don't I, got to know all this stuff.

I think it is a good idea to treat prophylactically with low dose Interferon should I ever be in need of immunosuppressive therapy...you have any studies on that...no, but it makes sense....maybe, you see me when you get a cancer. In the meantime I will look into that.

So you don't think I am talking of the wall...absolutely not, but you may have to pay out of pocket for Interferon.

I call that a forward thinking doc.

Thanks Tnguy, you know how much I appreciate your posts and links.

Ina

[Hepatitis Researcher]

HERE IS A BARE BONES VERSION OF THIS IMPORTANT PAPER

HUGE STUDY  NOT VERY GOOD NEWS

IT GIVES A NEW ARGUMENT TO THE DECISION MAKING PROCESS TO WAIT OR TO TREAT WHILE FIBROSIS IS STILL LOW

[chcnme]

I had no clue what PMBC was either and still don't know, but after I read the clinical trial, for me it began to take on the meaning, People Might Be Crazy.  Seriously though, I googled it, and it took me to

http://www.clinicaltrials.gov/ct/gui/show/NCT00188201

"peripheral blood mononuclear cells (PMBC)"

I'm feel like Bob (just not SVR).  Overload overload.  The  more I read the more confuddled I get.  I have a headache now, and I know now it's probably because the virus has crossed the blood brain barrier and is in my brain.  

Seriously again though - this is something for everyone to think about  (the findings of the study TNGuy posted), but I just don't think it's wise to try to apply the findings to.... nevermind.  I don't know what I think anymore.

[Moniker]

This is why we can't be organ donors or give blood - because of possible occult virus. But it shouldn't affect my own quality of life, and it's highly unlikely that I could pass hep c on to other people.

My PCR indicated clear <50 six months post tx. I feel very well now, better than before tx, and I don't have that old pre-tx fatigue. I'm glad I treated; my doctor said I'm "cured" of hep c now. I really want to get on with my life. I've got to stop thinking about hep c so much. I hope I can just move along to other stuff. Best of luck to all of us.

Bob

[sfbaygirl]

I just heard that a new article came out in Hepatology Magazine that deals with re-treatment and the low success rates. I haven't read it, but thought someone may have?

[cuteus]

TNGUY, is this the same study we read before?  it seems like it.  I know the significance of negative strands found, but what is the significance of positive strands?

[DoubleDose]

I agree.  Now, if only I felt that way!!!!

DD

[cigaso]

...or anyone. Please excuse my ignorance, but what are PBMCs?

[mikesimon]

It ain't over till it's over but when is it ever over?
I agree that it's up to us to be vigilant and get LFTs annually etc. but overall I think SVRs are in very good shape - as long as they feel that way.
Mike

[honey11]

yes I do feel fortunate to be SVR but reading this,,,always does make you wonder,,,what will become of us after being SVR say 5 to 10 years.  Really,,,it is something that we can not forget and I'm sure that all of us realize that we will always have an ongoing check in with our drs through the years and thats about the best we can do.  As far as leftover sides,,,knowing that others are experiencing same,,,this place is great for us to meet and keep up with ongoing health.  I have wondered also about transmission even though there is no viral load,,,I still am very cautious!

[HCA]

By coincidence I asked my consultant just this week if SVR's who subsequently required liver transplantation ever relapsed in the face of the immuno-suppressive drugs.He replied 'Surprisingly no!'
I wouldn't worry too much about this issue.

[Kalio1]

I think the research is interesting, but as the researcher himself says:

"persistence of HCV in these patients should be taken into account under special circumstances (e.g., immunosuppression or chemotherapy)."


unless we are in this situation or have these special circumstances, dealing with some other illness and/or treatments, this research does not impact someone who has treated their HCV and achieved SVR.

Even if you do end up facing a situation like this, it is still very very unlikely you would have HCV begin replicating again after acheiving SVR. We have enough to worry about as it is, no need to worry about this or worry that once you acheive SVR it might return, chances are very good it will not.

[fishdoc]

had to look this up: peripheral blood mononuclear cells (PBMCs), hmmm have to ponder the signifigance of lurking there as opposed to liver cells.........

[chcnme]

Hi TN.  I read some of the links you have provided here (someone put a URL up where you had given links to abstracts, etc.)  Great reads. Thanks for all you do.  

I talked to my doc a few weeks ago about this occult stuff, and he said they did one of the largest studies there (at Duke) on this and that yes -- it has been found in the livers of patients who are SVR but that it had to be looked for very hard (many many samples) to find it.  He didn't minimize the importance of this data but said that it needs to be put in perspective.  He put it in perspective for me by making the analogy that they can look at slices of breast tissue in breast cancer patients who have undergone chemotherapy and are in remission, and that they can find CA cells if they look for it hard enough.  He ended by saying that the very best thing a Hep C patient can do is to treat and achieve SVR regardless of this data.  

hmmm :) Interesting stuff.  

[DoubleDose]

You have voiced all of my concerns very clearly.  You make excellent points on each of these issues, and I am completely with you in feeling a great need for further study, better understanding of the implications of persistent HCV, and the development of more complete treatments or even a real 'cure' for this disease.

By now it should be plainly apparent to everyone on this forum that there is ample, and growing evidence that the virus is indeed NOT GONE after we achieve SVR, and is still replicating quietly in selected blood components, organs, and tissues.  
For people to assume that it will do no harm is really denial at its best, in that we have no clear idea of what the long term implications of this lingering viral state might be.

Sure, I want to be as healthy as I can possible be after my SVR, and do not want to obsess endlessly about the virus, but this information clearly puts us on notice that there is more after SVR to take into account, than was previously thought in medical circles.  We will need to know what we are up against, and we will need ongoing medical advances that will deal with these issues.

We also need to find out whether or not the virus continues to inhabit and replicate in other compartments after SVR, such as the brain, connective tissue, eyes, CNS, bone marrow, etc.  We really have no clear answers to these questions at this point.

An open question remains:  why do so many people retain severe fatigue related sx for years after SVR?  and other symptoms as well?

DoubleDose