Questionnaire

[TeeVee36]

I would like to know how many people have really been cured?  Specifically who is UND for 3 yrs or more?

Who has been UND for 6 mos to a year and then relapsed?

[nygirl7]

Good posts on this subject by Jim and Michael in the To Treat now or Later thread.

PErsonally I've been SVR over one year now, if that answers your questionnaire (even though it's not 3 years).

[Bill1954]

I'm still a work in progress :o), so I can't help with your questionairre; however there is a recent article in Clinical Care Options that discusses the term "cure" as is used in HCV management. Here's the addy:

http://tinyurl.com/2m9fwn

You'll probably be asked to register, but it's quick and free.

Best,

Bill

[jmjm530]

Studies have been done on the durability of SVR, which is really what you appear to be asking. Basically, if you're UND six months after treating (i.e.SVR) then your chances of relapse are only around 1%. If you're UND one year after treating, the chances of relapse approach 0%. I believe these studies go out 8-12 years for logistical reasons, but no reason to believe that SVR is not durable to these numbers for a lifetime. Personally, it's been almost two years since I stopped treating and I was UND as of one year ago. Not sure if I'm going to test again at the two year mark as statistically the chance of relapse are quite remote and last time I checked my ALT was 9.

-- Jim

[Bill1954]

Oops,

From the above referenced study:

"...Swain and coworkers evaluated 997 patients who achieved an SVR in trials that included treatment with peginterferon alfa-2a with or without ribavirin.[1] Patients were tested yearly by use of the Roche COBAS AMPLICOR HCV test v 2.0, with a reported sensitivity of 50 IU/mL. Over a median of 4.1 years of follow-up, only 8 individuals (0.8%) had evidence of recurrent infection. Although the details of this study have not yet been published outside of a conference presentation, the results are a welcome support for the body of data indicating that SVR is indeed equivalent to cure for most patients..."

Bill

[Deb_c430]

I a genotype 1a,  this is my third time txing.  

Last time I was SVR at 6 months,  that is 6  months  after finishing  tx 6 moths, at 9 months after I had relapsed.  

I am now on infergen

[jmjm530]

Here is the actual abstract from which the above quote was taken:
http://www.hcvadvocate.org/news/reports/DDW_2007/Abstracts/MondayAbstracts.htm

From the exerpt below, even the very low "0.8%" figure may overestimate the number of relapseers as one patient was a definite reinfection and it's unclear if some of the others were as well. Also, the issue of false positives is brought up.
---------------

"The author noted that of the 8 patients who became HCV positive during follow-up, that one was a clear case of reinfection because that patients tested positive for a different genotype than the genotype in the original study.

The authors are not sure if the other 7 patients are from reinfection or because the virus returned after therapy.   Another physician stated that because there is a 1% false-positive result that there cold be a possibility that the viral load tests have been false positive.  Unfortunately, those patients have not lost to follow-up. "  

  

[Deb_c430]

abstract or no,  I relapsed.

At  my six month  after tx i was still UNd, 6 months after that, still svr, then  at last 9 month follow up, I had a VL again.  

Follows up were all done,  healthy living,    Test were done and re done to make sure there were no false positives.  

Please do not genralize.    

[DoubleDose]

Your case is an example of why this subject warrants continued study!!!  The fact that ANY percentage of SVR's end up relapsing is a red flag in and of itself.  I understand, as Jim states, that maybe one or two were reinfected, but I don't think you can assume that all eight were reinfected.  If one takes this position, then they are using the same unscientific, conjecture-oriented approach that they would scold others for using in different circumstances.  My attitude is that as long as we see ANY recurrances of the virus after the one year SVR point, we need to be deeply studying and analyzing those cases, and fully determining whether they were indeed due to reinfection, or not.

If there is no evidence of reinfection, then the reason for recurrance must be discovered.  The exception to the SVR rule is a potential big red flag, and even though 99% seem to remain SVR (over a 10 year period maybe), we need to completely understand what that nearly 1%, or even just .5% might represent.  Only when these 'exceptions' to the rule are fully explained, and demonstrated to NOT BE an internally generated recurrance (relapse) of the virus, will we be able to use the word "CURE" with absolute confidence.  

Also, we need to ultimately understand whether this is a virus that is capable of being totally eradicated, or whether it becomes more of a "dormant" virus, or goes into more or less permanent remission.  If the latter is the case, we would want to better understand what might possibly trigger a recurrance of the virus.  If the former case is true, we would have no concerns about having a relapse from ANY cause, other than a new infection.

The JHH department head that authored the article discussing 'cure' (referenced above)also seems to hedge a little bit, here and there, in not saying for sure that some of these cases were not due to a true relapse.  I think he leaves that question open and unanswered.  We are again left with the pragmatic definition of "cure", with the small letters....which is:  almost everyone who gets the SVR remains SVR for periods of 2 years to in some studies up to 10 years.


That is my read on the current definition of 'cure' as relates to HCV....nothing more, nothing less.  I am fine with that, and enjoy the fact that we obtain many benefits from being SVR.  I am still curious as to whether and why there seem to be 'some' cases of unexplained relapse.  Yours is a good example Deb!  We have heard other anecdotal accounts of this happening to others, but I would doubt that they were intensively analyzed.  Some of these cases may go beneath the scientific radar screen.  Others may just be 'assumed' to be reinfection, or improper testing.  Assumed.....Assumed...

DoubleDose

That's my take anyway!

DoubleDose

[jmjm530]

I'm very sorry about your relapse, but if you read my previous posts you will see that I did not "generalize". What I said was that studies showed that around 99% of those who were UND six months post treatment remained UND and this seems to be born out by the collective experiences here. It appears you are one of the unfortunate 1%.

There is also the possiblity, although statiscally very low, that one of your two tests was wrong -- either a false positive and/or false negative, with the former more likely.

Hopefully, you re-tested after your 9 month follow-up to make sure it wasn't a false positive. We have had cases here of false positives following EOT that on re-testing turned out to be UND.

-- Jim

[desrt]

Undetected since January 2003. Ended treatment April 2003. Last tested undetected April 2007. Fired as a patient by my gastro January 2008.

[Deb_c430]

I totally agree with all your points.  so far SVR is theory and that is all, if your antibodies do not  disappear, it seems that  like chicken pox,  they can mutate, they can become something different, like chicken pox  lies dormat and in older people becomes shingles.

I think people like to put things in nice little boxes, but this is a virus,  with virsus be it flu, chicken pox, they mutate. They lay dormat,  they become something else sometimes,   If we are lucky they stay dormat.  There are no absolutes.

It is still all theory, NOT fact yet. % do give us a clue.   For most I pray they hold accurately!  That those who are SVR stay that way!

I do not see SVR as cured, I see it as remission and hopefull with long term effects!

The fact is I would have been a perfect canidate to find out why, I have never been a drug user, nor a drinker,  I am healthy always been so. My test have been done and re done 1000 times ( Iexagerate) But no one was more surpirsed  than GIs. Except me!

The only thing anyone could point to was for part of treatment I was on steroids, but so low a dose and was weaned  in the first 4 months, I txed for 48 weeks.

So thank you Double,  that made sense to me, and I agree with it 100% ,  

Deb

[Deb_c430]

sorry but all my PCRs were done twice, so no there was no " mistake" in  the tests. Why they were done  twice was because of steroid concerns even then.  
Also other concerns,  so yes in my case you are not correct.

[jmjm530]

Please, I didn't say your tests were wrong, I just offered up some possiblities based on actual experiences here. As stated, being UND at six months is not 100% guarantee of SVR and no one has said that.

I realize that's no consulation to  the 1% or less like yourself  that do relapse after six months, but it is a consulation to those entering treatment to know that SVR is durable to around 99% or better, depending on the study.

-- Jim

[Deb_c430]

That I will agree with, but as double stated,  there are I think more of us than you would think.  I only began coming to this   forum to find answers.  AS relapsers.

I would even suggest there are many who do not even know they have relapsed.  

I think I stated quite clearly I hoped this was not true for anyone else NOR  do I hope it is.

[Mr Liver]

deb,

I'm a 2 time relapser and I understand the disappointment one can feel all too well. I hope your future allows you to attempt again with one of the newer meds coming to market in the near (3-5 years) future.

I do have to disagree with you on a couple of points. I only do so because I feel this is a topic that is extremely important to get right, according to the known facts.

"I do not see SVR as cured"

I'm  curious as to when someone who is undetectable for HCV gets to use the word 'cure' ? Never ? That hardly seems fair. Even cancer patients get to use the word after a set amount of time has passed according to their type of cancer. There's never been a documented, verifiable, proven case of relapse beyond 3 years. Never.

You stated that SVR is just a theory. Actually, HCV lying dormant is just a theory. And with no proof of any kind to support it. On the other hand, durable SVR is a fact, born out by 12 year followup studies. In addition to that, post-mortem autopsy studies have shown the absence of detectable virus in some who cleared HCV infection through tx.. Viremia was not present in the sera as well as in the rest of the body, including the liver, of course.

I agree that many people do not know when they actually relapsed and some aren't aware right now that they have. That may be the case with you, as well. You may have relapsed right after 1 year post-tx and didn't discover the fact until 9 months later. So you may have, in reality, relapsed at 12 months, which is not very common, though not unheard of either. Appx 2-3% relapse after 1 year and over 99% of the remainder will remain SVR.

I have a friend who cleared on IFN monotherapy 14 years ago. Personally, I think he has every reason to use the word 'cure' to describe his eradication of the virus.

Antibodies do not mutate. The virus does, with HCV being the fastest mutating virus known. However, 99.99999 % of all mutations (quasi-species) only exist a few seconds to a few minutes. Wild-type virus lives just a few hours. (about 5). This seems to suggest that laying dormant would lead to the virus dying off rapidly through attrition. Another reason to doubt that theory concerning dormancy, in my opinion.

regards,
Mr Liver

[mamakat3]

I'v been clear since ending treatment 11/04... so about 31/2 years.  Still scared ******** sometimes that it is going to come back... other times i KNOW it is gone forever... Eating good, living right... that all helps.
k

[Deb_c430]

Well that makes sense to me,   but I see this as a virus again much like chicken pox.  Again this is MY theory.  

I am not trying to take away anyones joy at SVR, or cure or remission.  But I do not think all the facts are all in yet,  that was my point.    

Antibodies may not mutate, but they do remain, and as long as they are there I do not trust them, again MY theory.  

Because my Docs tracked me so closely I can pretty be certain when I relapsed.  
I would maintain there are many out there not posting on this forum or who have  SVRed that have not re tested or followed up that have rrelapsed.

I have treated three times now, currently I am on infergen daily, ribo, and all the rescue drugs.    

This is not a sour grapes theory at all, this are my  and some  very good Doctors, I have met with, concerning this. while I may be generalizing their words a bit.  I feel there is a lot more to research to be done for relapsers and non responders.

I totally agree the facts need to be right, to include us.  

You are very gentlemanly and I  thank you for not patronizing me.  I very much enjoyed reading your post.  And the spirit in which it was given.

Deb

[DoubleDose]

I will take a stab at your question, regarding '  when do we get to call someone cured that has achieved and maintained SVR.'  First, I still am comfortable with using the term "cured", as a technical description for almost all SVR's.  The small letters indicate that it is not a declaration of formal, total, unequivocal eradication (Cure) of the virus, but a sort of practical working definition for 'cure'.  I think this terminology allows room for miniscule error in the 'absolute' nature of the term, and also forgives the small percentage that actually do relapse later than the six-month rule.

Now, when can we use the term "Cure", as in gone, eradicated, and never will return without outside infection?  Possibly you could define a time period, maybe three years, maybe five years, in which, if no other SVR's are found to EVER 'relapse'  beyond this point without being reinfected, then this could become a 'cutoff' point, and could then go from being a 'cure' to being a 'Cure!'.  If we become certain, through tracking, and rigorous follow-up studies, that literally NO ONE really ever truly 'relapses' after a certain point, then we might be able to have a viable concrete definition for 'Cure'.  

Currently, with some evidence of late relapsers, beyond six months, or one year of SVR, I think we have to be content to use a compromise term like 'cure*', maybe with the asterisk, and wait to learn more before assigning a hard and fast point for  true 'Cure' status.  

What do we do if we turn up a few who truly relapse after six or eight years, as the couple of cases were reputed to be in the immunosuppressive drug incidents published in the past few years?  We don't know all the real details of these cases, but if they turned out to be true, then I feel we would have to remain using only the 'cure*' terminology.

I just think we need more definitive study on the issue, a consensus of results, and full agreement that there either: can be, or cannot be, late relapse, without having been reinfected.

At the same time, there is a question in the definition of 'Cure' as to whether that should also mean that problems resolve, or symptoms go away.  How about spontaneous clearers of the virus, who have been found, by and large, to be very symptomatic many years down the road?  They only had an acute, brief HCV infection, and their immune system cleared it, and in effect 'Cured' them...or so it would seem.  But if they indeed suffer from the same symptoms as HCV+ individuals, decades down the road, after clearing the virus....do we consider THAT cured???  Just clarifying the underlying assumptions underlying the term 'Cure'. How about SVR's with the same long term extra-hepatic symptoms years after SVR?  Is that fully 'Cured' also???  These are questions for everyone to ask themselves, not answers.

Just a few more thoughts.

DoubleDose

[sldb]

18mths post tx und. and i cannot bring myself to utter the word cured. I will feel more comfortable at 2yrs., but i might find a place in my vocabulary for THAT WORD  5 yrs. post tx. Iam just happy for what i have right now.....

[Loddfafnir]

Just had a physical last month and I'm still SVR after more than four years.  My doctor told me I was 'cured' after being SVR for two years and I'm not too concerned yet mentally when it's been five years I think I'll be finally convinced it's gone.

[Mr Liver]

You have my best thoughts for a successful conclusion to your treatment this time. I truly cannot comprehend doing interferon/riba daily, and I hope that the effort it must take results in a positive outcome for you.

"I would maintain there are many out there not posting on this forum or who have  SVRed that have not re tested or followed up that have relapsed. "

I'm sure you are right. From a statistical point of view there has to be people that fit your description above. Obviously, those who do not have another followup beyond 6 months post-tx contribute the largest share of those who have relapsed and are not aware of the fact. I'm not sure just how prevalent this subset of those who SVR and relapse after EOT without awareness of the fact, are. Whatever this number is, one has to consider that the majority of them never would have needed tx in the first place. This diminishes the significance of relapse in the overall population greatly, although this is rarely mentioned.
I wish I was in that majority, but like you, I have not been able to eradicate it.Yet. :)

regards,
Mr Liver

[Deb_c430]

Double thanks,  you always find the way to clarify what I am trying to say!    I know what I mean but often I can not the correct words.  

I think that this virus is wiley,  I know people who have had cancer, had huge chunks of their bodies cut away. Been radiated, chemoed,  "cured" then 8 years later it has returned. Surgeons will tell you, there is no way they can be sure 100% it has all been cut away.

I do not understand that cancer and hcv are NOT the same things.   But I think in my case a there was a little bit of the virus "hiding" out.  So the same theory applies.

Mr Liver, thank you again,   as hard as this is, it is doable,  infergen does not stay in your body like Peg,   I am thinking if this time I do not go UND, then SVR,   I will try one more time the alinia. But that is not for sure either.  I truly do not want to spend  the rest of my life sick, I want to enjoy a good quality of life and  enjoy my family.

I wish you all the best, mr Liver.  

With kind regards

[TeeVee36]

Thank you to everyone, I got all of the information I was hoping to get.  Some GREAT and some not.

I am nearing the end of my tx and am getting excited about just being done.  I don't ever want to take it again.  I just wanted to get a feel for the success rate.  My doctor discouraged me by telling me that the 50% success rate of people being 'cured' included all of the people that finished tx and were SVR and then relapsed.  Then when you read about people relapsing on this forum it can be discouraging.  

Personally, I am going with the 1 yr mark.  If I reach SVR 1 yr post tx then I am going with 'CURED'!

Thanks again,
TV

[mikesimon]

I have told this story before so I apologize for being repetitive.

I was transplanted in June 2000 for HCV. I treated two times - the first TX I was never undetectable due to low doses of both TX drugs. The second time I became undetectable late in treatment and relapsed when I stopped - I believe the relapse was because my ribavirin dose was inadequate.

Then I treated for 73 weeks with optimal doses of both TX drugs and became undetectable by week 11 or 12 at the latest. I stopped TX in June 2004. I have always tested monthly with Heptimax tests < 5 IU/ml and have been undetectable since April 2003.

In late April my anti-rejection drug was drastically reduced (my center tries to reduce these drug doses and in some instances completely ween patients off, if possible).
My enzymes, which had been in the teens since 2004, suddenly began to elevate rather rapidly. We continued the reduced anti-rejection dose and watched my enzymes continue to elevate with the hope that they would settle down. I became alarmed and called my surgeon and he ordered a liver biopsy. I had one on June 3, 2005. This was on a Friday.

The following Monday morning I was in my surgeon's office and he was looking through my chart. He said: "it looks like hep c to me."
I asked him what he was looking at and he said "your labs".
I said "what about my biopsy" and he replied that he'd been in South America and just got back so he didn't know I'd had the biopsy. The nurse found the report and showed it to him. He said "yes, it's hep c".

I was floored. I had been undetectable for well over a year and off drugs for just weeks short of a year. But, he wasn't the least bit surprised and, in fact, could tell from my labs and the enzyme increases that it was related to HCV. The biopsy merely confirmed what he'd already suspected.

My biopsy showed HCV in my liver at a very low viral load - 30 IU/ml.
I asked him how this could be. He said that when my anti-rejection dose was reduced it stimulated my immune system and that it began attacking the tiny bit of HCV in my liver and in the process bystander cells were attacked - a sort of biological collateral damage - which was reflected in my soaring enzymes.

I was torn because I had been afraid that I was rejecting my liver so it was a relief that I wasn't rejecting but, the fact that HCV was detected in my liver was a total surprise. I never even considered that possibility. I thought I was completely clear - after all I tested monthly with a very sensitive test. I had tested undetectable just a week or two before my biopsy and, incidentally, again 2 weeks after my biopsy - which was also undetectable.

I asked my surgeon what percentage of the non transplant population SVRs did he believe would show HCV on biopsy. He said about 75%. I asked him if it was like my immune system and the HCV had entered into a truce that got broken when we reduced my anti-rejection dose. He replied that I could look at it that way if it helped me to understand it. Then he said a couple of things that I found intriguing - well, I found all of this stuff intriguing to be straight with you.

He said that my center likes to reduce immunosuppressive doses but with HCV patients it's very tricky. It's quite different with transplant recipients with other underlying diseases but with HCV transplants they often run into problems.
Then he said: "When we completely eradicate every trace of HCV in a patient we frequently run into organ rejection issues". I asked why he thought that was. He responded that perhaps the virus has immunosuppressive properties - that perhaps a little HCV is good for me.

I think that one of the salient points, aside from the obvious ones, is that my surgeon wasn't the tiniest bit surprised to find HCV in my liver. It was like "yeah, it's HCV".
I would guess that the fact that I am immunosuppressed might be viewed as a distinguishing factor which makes my experience unique and not applicable to the general population. Perhaps that is true to some degree. But, how many SVRs undergo biopsy? I doubt there are many and I also doubt whether a typical doctor would look for HCV in an SVR biopsy or detect it.

The other interesting point was that my surgeon noticed an increased incidence of organ rejection in those patients who appeared to have eradicated every trace of HCV with treatment - that it may possess immunosuppressive properties or or effect an immunosuppressive response.

I personally believe that we can use the word "cure" notwithstanding the possibility that some degree of viral activity may still exist in some or many SVRs. I think that SVR has been proven to be durable and it certainly confers tremendous benefits to those of us fortunate enough to get there. I don't rule out extra hepatic issues that might exist post SVR in some or many of us and I too would like to see more research into this area. I do believe, however, that the focus of research should be trying to get better approaches to allow more people to achieve SVR with less treatment related sides and persistent health issues caused by current treatment. Once we get a better grip on those issues then maybe more attention will be focused on the issues that DoubleDose is concerned about. I certainly think they are important issues that do need to be addressed.

Mike