Hepatitis rebound seen after treatment 'success'

[l-horn]

I
Reuters Health

Tuesday, November 7, 2006

NEW YORK (Reuters Health) - Hepatitis C virus (HCV) can persist and replicate in the livers of patients who have apparently cleared the virus from their blood after antiviral therapy, a study suggests.

Previous studies have identified HCV in liver tissue of patients with a sustained response to anti-HCV treatment. However, it was unclear if viable HCV, capable of replication, was actually present.

In the present study, Dr. Vicente Carreno and colleagues, from the Foundation for the Study of Viral Hepatitis in Madrid, Spain, tested HCV in hepatic tissue taken from 20 patients who had shown no evidence of the virus in blood for 35.4 months on average.

Nineteen of the 20 samples contained "positive-strand" HCV RNA, the report indicates. Moreover, of these 19 samples, 15 also had "negative-strand" HCV RNA, which is capable of replicating.

Testing of peripheral blood mononuclear cells revealed positive-strand HCV RNA in 13 of 20 samples. Twelve of the 13 samples also contained the all-important negative-strand HCV RNA.

The post-treatment liver biopsy specimens of 15 patients still displayed signs of liver damage. However, hepatic damage improved in all but two of the patients.

The findings indicate that "these patients did not experience HCV infection clearance, despite apparent clinical disease resolution," the researchers conclude.

They say the possibility of HCV reactivation should be borne in mind if patients undergo chemotherapy of become immunosuppressed, for example. The team cites a case in wh

[DoubleDose]

Another study that raises concern about the potential for reactivation of the virus!  I would guess, that if these studies are accurate, then we would consider the virus to be in 'remission'.  I am not sure that even that description is accurate, since it appears there is still an ongoing infection, and some chronic evidence of the virus, albeit without the same sort of ongoing, progressive damage as the 'active' form of the virus.  I hope they figure out real soon just what the ramifications of this 'residual' virus might be, and just how possible it might be to reactivate it.  This sure makes me concerned about any immune system modulating medications, and also about what effect drinking any alcohol, even in small quantities, might have on the virus remaining in the liver.  Could it act as some have described in the past with the active virus:  throwing gasoline on the fire????  Could it provoke an upsurge in the low level persistent copies that could push it over the line back to an out of control, active infection?

I really do NOT like to read these studies, but being a brutal realist, I really need to know what is going on.  I want to be prepared to deal with it, and also to understand what else might be done, far down the road, to possibly get rid of the remaining residual infection.

Also, I would ABSOLUTELY love to see all these research studies discredited, and proven false...but I have not seen any proof to the contrary yet on any of them.  The only replies from the medical community on the other side of the fence are statements like:  well it must be testing errors, or cross contamination...(with WHAT????), or they must be remnant copies that are deactivated (how come they are replicating???)etc. etc.

Its potentially not really as disturbing as it seems, because in the best case, maybe we can live a healthy life with the virus in 'remission'and have no further problems......OR, in the worst case, maybe the lingering infection does its own ongoing damage by provoking our immune systems, or even causing chronic, low level damage on its own.  Do we know for sure that none of this persistent stuff is still lingering in our brains, our CNS, our joints, eyes, etc??????  It will be interesting for sure to see what ultimately shakes out of all of this.

One final comment:  I always wonder why so many of us 'cured' SVR's continue to spend so much time on forums, and doing research.  If I truly 'felt' cured, and 'good to go', etc. I believe that I would be on with my life, with little need or use for research or forum talk.  I think that I, like many others, still feel 'ill effects' of a wide variety, and that we are still searching for our real 'cure'.

That's my opinion anyway!

DoubleDose

[NYgirl]

I plan on spending a bit of time once in a while coming to the forum to help out new people once I am done with treatment - but certainly NEVER would I spend all of my time on here reading and writing.

As time goes by new people become old timers and are equipped to deal with the questions that come up. it's important that they do this! It's sort of the "cycle" of how things go.

As long as they are there to provide the valuable input...it's not necessary and I intend to live my FULL life.  And that doesn't include internet forums at all...not when I can go out and eat at a restaurant (ha EAT! at a restaurant! what a CONCEPT?!!!!! or do something else OUTSIDE my bedroom. WOWOWOW! I can't even imagine that anymore and I used to be such an extreme extrovert and NEVER at home. Now...you'd have to pay me to leave the house just about!)

"Cured" is a hard word to use when someone has SVR yet posts all day every day on tons of internet forums I really think. a major portion of this disease is mental and that aspect must be dealt with as well you know?

I hope I can do it.  Of course I'm not sure. But I am going to try and get my life back as much as I can. That doesn't mean though I won't come in and check on people at stuff...there is a big difference, I'm sure even though these words don't all sound right you know what I mean and am trying to say.

I'm just a spazz and nothing ever comes out right no matter how hard I try.

Edgar Allen Poe I'm not. ;)

[mikesimon]

It's easy to have a clear plan. Execution is another issue entirely.

[cuteus]

this study was already posted and discussed when tnguy linked it.  old news.

[jaroman]

I agree that once finished with tx, we should try to go on and let others help newcomers.  BUT, I feel like I will always be a hepper-esp. since I think the virus is always there in me somewhere. also, almost every time I get on here, I learn about newer studies, etc.

[DoubleDose]

Here is a pasted paragraph from the HCV Advocate Newsletter:

Some experts have gone so far as to describe post-transplant HCV recurrence as “universal,” but here again, data are mixed. It is evident that many patients who achieve sustained virological response (SVR) with interferon-based therapy prior to transplantation still experience viral recurrence. This indicates that a low level of HCV genetic material remains in the body waiting to “seed” the new liver, even if it is undetectable using standard tests. As reported in the January 2006 Journal of Hepatology, for example, Martina Gerotto and colleagues found that 26 of 208 hepatitis C patients (12.5%) who had repeatedly undetectable HCV viral load at the end of treatment using common polymerase chain reaction (PCR) technology still had residual detectable HCV RNA using a more sensitive transcription-mediated amplification (TMA) assay


My comments:   More of the same issues being raised....yet why do our HCV doctors act as if this stuff is alien to them?
It looks pretty well studied, and understood by the liver transplant community.

DoubleDose

[cuteus]

so which one is it, 90% of SVRs or 12%?  and you wonder why some drs are not ready to embrace the residual virus theory completely?  depending on which Spanish study you read, you get a different percentage.
If they are using the same tests that scubadiver was asking about, no wonder, what did his dr say? a PCR is a PCR?

[returntosender]

I had a pretty dark disturbing thought about relapsing that this thread reminded me of - and before I say it I will enter a disclaimer that I immediately dismissed it and that I would trade relapse for SVR anyday - but I actually had a thought that things I dont have to worry about anymore -- relapsing -- occult virus -- residual virus -- cure -- autoimmune hep -- yearly PCRs -- scary phone calls -- not feeling good AFTER clearing the virus - none of that matters anymore.  

It sounds crazy I know and I dont mean to minimize this but I really had this crazy thought that the pressure was off.  I gave it my best, followed the rules and followed the threads, shot my shots, swallowed my pills, drank the water and rubbed on the lotions, and ate drink and slept recovery for 18 months.  I am tired.  Tired of being freaked out and wondering when the shoe will drop and wondering when the syptoms (symptoms) will end.  Dont hold it againast me, its probably just the virus talking, I have relapsed you know. I am one of the lucky 50% who can relax. See what I mean, pressure off! LOL

[DoubleDose]

Darkly funny as you said.  But, you know what....it makes some sense.  At least when I was treating I was aiming for a goal....and feeling optomistic every day....and I got to that goal....and...and....guess what?   All the articles started covering 'persistent HCV', residual virus, SVR not being a real cure, watch out for re-activation, will you get HCC after SVR, interferon damage, compartmentalized virus, lymphatic system harboring different strains of HCV after SVR,...and on and on, and on....just like today.  Its not all the fun its cracked up to be, being SVR!!!!  But I'll take it, and you will too, when you do your next round.  The dark humor is good for now, and its really on target....but you're gonna get the SVR so you can worry about all the *#*@## that I do everyday!!!!!
Its only fair.

DD

Hope you are doing well!

[chcnme]

You bring out some good points, DD. The findings in that study are disturbing.  I've not been able to find much since it was published to convince me the findings are nothing at all to be concerned about except for a reply from a leading Hep C doc to someone who inquired about the study and asked him if it was anything to worry about.  He essentially said we have nothing to worry about. I am not pro treatment; I'm not anti treatment; I just try to gather all the information I can so that I can make an informed decision while "watching and waiting".  I'm glad I'm able to do that for now (the watchful waiting.)  I'm going to see my doc tomorrow, who is also a leading doc in the treatment of Hep C, and I'm going to mention this study.  If he says "no worries", I'll have to trust him, but still -- the findings concern me, as I know they do many others.  I guess the best we can do is what the experts say we should do. But still .... (oh the "but still" syndrome)

[l-horn]

...The team cites a case in which HCV reemerged following prednisone therapy, after 8.5 years of negative test results.

[mikesimon]

I think that the word "rebound" in your title is a bit misleading. The virus doesn't rebound - it was always there. "Rebound" suggests an increased VL which isn't the case absent reactivation or a new infection. Mike

[beamishboy]

between the idea and the reality  lies the shadow

[jmjm530]

OK. Assuming persistent virus exists in such and such a per cent of SVRs. Correct me if I'm wrong, but didn't DD recently say that persistent virus is "benign" without symptons, and the real concern is with "occult" virus, which has nothing to do with SVRs? So if persistent virus is benign,  and basically there are no cases of viral reactivation (relapse) after one year successful EOT, then what exactly is the concern?

[DoubleDose]

chcnme:   Although these studies are very disturbing on an individual basis, when you look at relative benefits or disadvantages, I have to take the position that treatment and SVR trumps the possible downside of SVR with HCV persistence.
At least treatment does seem to produce a durable SVR (even if we remain infected at a very low level), and treatment often stops the ongoing destruction of our livers.  Preventing premature death is still the over-riding goal of therapy, even though it may not be a total remedy, or a miracle cure.  It all comes with a price, and we all have to be willing to take that gamble, and hope that the ultimate benefit far outweighs the negative consequences.  Also, it is the only, and the best thing that we have going for us at present.  We may never get a total cure, and even the next generations of medications may end up doing no more than putting the virus into remission, or even just keeping the levels very low, with less side effects.  I guess I am still pretty 'pro-tx', and since I did it two long drawn out times, I had better be pro-tx!  Only in exceptional cases would I advise waiting for long.

Cuteus:

I know that the percentages vary from study to study, etc.  But just pointing that out does not cause the data to become invalid.
Often the tests they use to detect the residual virus vary quite a bit in power, and amplification level.  Some of the higher amplification testing finds much higher percentages of replicating HCV in the tissues, and the lesser amplified tests seem to find fewer positives.  Still, the data seems to be pointing in one direction....and not a great one.
We can ridicule the researchers, or their backgrounds, if that takes away the concerns we have about their results....but I fear we are not going to be able to derail this freight train as the research studies become more widespread, and accepted.  And why should we try, if they are valid?  I just want to see the unbiased results of all the ongoing studies.  The truths about HCV will assemble before us, on their own. Nothing can stop it.

DoubleDose

[prettydamscared]

I asked my doc about it today and he is a fairly well known,  big name kind of guy from a major teaching hospital.  I appreciated that he didn't dismiss the studies but did say basically that other than the three main studies that we already know about, there isn't enough data to form any conclusions.  He did add that if the studies are accurate, "it is what it is", i.e. if occult or persistent virus exists in SVR's, what can we as patients do about it at this point?  I think just take our svr's and be happy for that, at least.  I don't mean to minimize any of this and I'm not quoting word for word, but I think I'm imparting the gist of what he said, for what it's worth.

[FlGuy]

'..Some experts have gone so far as to describe post-transplant HCV recurrence as “universal,”... I don't believe that is at all a new concept.  Mike has relayed the same statement on many occassions.  If I recall correctly, Mike used the term 'invariably' in place of 'universal', but simiar level of certainty.

[DoubleDose]

Essentially what I just said above to chcnme.  I agree.  I just get a little concerned whan people want to discredit research findings, because they do not like what they imply, rather than find out whether they are valid or not.  I think we all need to keep completely open minds, so we can deal with the virus, and its ramifications, as it really is.  Not as we pretend to ourselves that it should be.  I say keep asking questions, and keep finding newer answers.  That is the only way to ultimately conquer this disease.

DD

[FlGuy]

Haven't seen you in a while. May be I'm not as attentive these days but hope things, on all fronts, are looking up for you these days.  You had some rough time for a while.  Take care.

[prettydamscared]

Hi, You're right, I haven't really been posting but starting reading the board again a few weeks ago.  I'm doing much better now.  First 12 weeks were a killer but I've had 4 shots of procrit and the rash is gone so life is as good as it gets on treatment.

Congratulations to you!  You were UN at 2 weeks using a test with a sensitiviy down to 50, was it? The more I read about your doc's practice, the more I like it.  I'd like to know exactly when rescue drugs would be presribed, as you did. I also really like that you get your labs instantly.  Your doctor seems to have used the "sledge hammer" approach to knocking out your virus, but within reason.  It sounded do-able and it's worked so far.  That's as good as it gets, right? So, how are you feeling this time around, so far?

[prettydamscared]

I completely agree with you.  Your post to me was well put.  I am following your posts and thoughts regarding these studies with a great deal of interest and appreciate your calling them to our attention.

Char

[moveabove]

You can search the web for almost anything.  Look at Loosechange2 its a google vidoe, Look how well its done and the facts it brings up.
I am going to stick with what my doc says and the two people I know personaly that went though tx and are cured.
  Just like its a fact that so many people onhere are so quick to recomend Ad's, I am sure that most people who go through tx, having it a sucsess then get reinfected, are doing the same old behaviors.  Im not saying all, of course but to put a "study" on here and not knowing the facts is silly.
  Just as transmitting,  Its not sex silly, its the other partners, behavior.  DIG IT?
I am undected since week 12 and if I dont shoot drugs or some of the other stuff I used to do, Ill see you in 25 yrs and still be undected

[illo]

I guess there are no guarantees in life.  I agree w/NYgirl. Live life the best you can. I've driven myself crazy for over 4 years dealing with this dragon, and I'm getting to the point that I'd better put it on the shelf and start to live again.  It's difficult to do when you are taking pills (herbs & supplements) all day, some with food, some without food, early AM, before you go to bed, etc, so it is quite a challange to ignore the fact that the HCV is there and to try to 'live normally'.  I am doing my best and I think living life in spite of illness or situation is the lesson for me.