Relapse Rates in Correlation to time after SVR

Hi,
I am looking for good links to scientific data about the correlation between relapse rate and time after SVR. I think someone has done a study to find out, how many of us stay "clean" after SVR. My sugestion is, if you are UND 6 month after last shot, you have a good chance to stay forever. But how big is the chance? It should be better after 12 month than after 6 and even better after 3 years than after one year, and so on.
Well, are there any data availabele on this time dependency somewhere?

Drofi

[drofi]

forgot to say that finding some occult RNA in mononuclear cells after SVR is a big point of fear in Germany because of recent publications:

Journal of Virology,
November 2006, p. 10972-10979, Vol. 80, No. 22

Cellular Immune Responses Associated with Occult Hepatitis C Virus Infection of the Liver

Juan A. Quiroga, Silvia Llorente, Inmaculada Castillo, Elena Rodr

[jmjm530]

Studies suggest SVR is durable to 99% or more, after being non-dectible six months post treatment. Because SVR is a relatively recent phenomenom, these studies only run 5-10 years but there's no reason to assume that SVR is not durable beyond that.  When you say "occult" virus after SVR, I think you mean "persistent" virus. My understanding is that occult virus is defined as those who are both PCR and antibody negative but still show virus in other compartments. Both occult and persistent virus are somewhat controversial issues and to the best of my knowledge, the clinical significance of either is still unknown, i.e. there may be none. Could you be more specific when you say this is a "big point of fear" in Germany. Is this something your doctor(s) told you, or just your interpretation based on the studies presented. BTW if you have the links to the studies please post.

Be well,

-- Jim

[jmjm530]

Said prev: My understanding is that occult virus is defined as those who are both PCR and antibody negative but still show virus in other compartments.
------------------------
These individuals with "occult" virus therefore have not been treated for Hep C. Since they haven't been treated, they can't show virus after SVR because there never was an SVR as commonly defined.

[FlGuy]

"... let's stick to science and what we actually know, not what we as patients want to believe...."


"The commonality of the residual sides of treatment have NOTHING to do with old age, or whatever else people here foolishly ascribe the symptoms to and have everything to do with the combination of HCV, peginterferon and ribavirin."

Given the science reference in the first sentence, where's the science applicable to the second?

[drofi]

Here is a link to the papers about occult RNA. I didn't ask for opinions, I asked for scientific data, please have a look to the start of the thread.
http://www.mediwiss.de/Langzeit.htm

Drofi

Cellular Immune Responses Associated with Occult Hepatitis C Virus Infection of the Liver
Abstract - Journal of Virology, November 2006, p. 10972-10979, Vol. 80, No. 22

Hepatitis C virus replicates in the liver of patients who have a sustained response to antiviral treatment.
Abstract - Clin Infect Dis. 2006 Nov 15;43(10):1277-83

Combined Hepatitis C Virus (HCV) Antigen-Antibody Detection Assay does not Improve Diagnosis in Seronegative Individuals with Occult HCV Infection.
Abstract - J Clin Microbiol. 2006 Oct 4;

Virus-specific T-cell responses associated with hepatitis C virus (HCV) persistence in the liver after apparent recovery from HCV infection
Abstract - J Med Virol. 2006 Sep;78(9):1190-7.

Long-term outcomes of chronic hepatitis C patients with sustained virological response at 6 months after the end of treatment.
Abstract - World J Gastroenterol. 2006 Sep 14;12(34):5532-5.

Late spontaneous elimination of HCV-RNA from mononuclear cells derived from peripheral blood in patients with chronic hepatitis C
Abstract - Przegl Epidemiol. 2006;60(1):79-85.

Correlation between beta-lipoprotein levels and outcome of hepatitis C treatment
Abstract - Hepatology, Volume 44, Issue 2 , Pages 335 - 340, 26 Jul 2006

Detection of Hepatitis C Virus (HCV) RNA in the Liver of Healthy, Anti-HCV Antibody-Positive, Serum HCV RNA-Negative Patients with Normal Alanine Aminotransferase Levels
Abstract  - J Infect Dis. 2006 Jul 1;194(1):53-60
Full Article - Fundaci

[drofi]

You wrote: Studies suggest SVR is durable to 99% or more, after being non-dectible six months post treatment.

Which studies? Any citations or links? dependency of time? Is itbreally 99% afetr 6 month and is it 100% after 3 years? Are there any SCIENTIFIC studies?

Regrads, Drofi

[drofi]

The  spanish study: RNA after SVR

    Hepatitis C virus replicates in the liver of patients who have a sustained response to antiviral treatment.

        * Castillo I,
        * Rodriguez-Inigo E,
        * Lopez-Alcorocho JM,
        * Pardo M,
        * Bartolome J,
        * Carreno V.

    Foundation for the Study of Viral Hepatitis, Madrid, 28015, Spain.

    BACKGROUND: Positive-strand hepatitis C virus (HCV) RNA has been detected in the livers of patients who have achieved a sustained biochemical and virological response to antiviral therapy (hereafter, referred to as sustained responders), but negative-strand HCV RNA was undetectable in the hepatic tissue of these patients. We studied the presence of both positive- and negative-strand HCV RNA in the livers of 20 sustained responders with chronic hepatitis C whose response persisted for a mean (+/- standard deviation [SD]) of 47.4+/-32.8 months after treatment. METHODS: HCV RNA was tested by strand-specific, real-time reverse-transcriptase polymerase chain reaction and by in situ hybridization in posttreatment liver biopsy samples (obtained a mean [+/- SD] 35.4+/-35.0 months after therapy) and in patients' peripheral blood mononuclear cells. RESULTS: Positive-strand HCV RNA was found in 19 (95%) of 20 liver biopsy specimens, and negative-strand HCV RNA was found in 15 (79%) of the 19 samples that had positive-strand HCV RNA. These results were confirmed by in situ hybridization. Regarding peripheral blood mononuclear cells, 13 (65%) of 20 samples had positive-strand HCV RNA, and negative-strand HCV RNA was detected in 12 (92%) of the 13 samples with positive-strand HCV RNA. Liver necroinflammation was still present in the posttreatment liver biopsy specimens of 15 patients, and fibrosis was present in 7, although liver damage improved in all but 2 patients. CONCLUSIONS: HCV persisted and replicated in the livers and peripheral blood mononuclear cells of most sustained responders. Thus, these patients did not experience HCV infection clearance, despite apparent clinical disease resolution.

    PMID: 17051492 [PubMed - in process]

[jmjm530]

Rev: There is also no reason to assume the durability of a SVR lasts any longer either. Is there?
-----------------------------------
Hopefully, I made the distinction of fact and opinion clear. The fact is that the studies are 5-10 years out. My opinion is that by standard definitions SVR will be durable longer than 5-10 years out.

Speaking of opinions, your opinion that the current drugs will be trumped by something else. This is not fact either. However, it is an opinion which I happen to agree with.

As for your statements regarding the toxicity of current treatment and residual side effects, I happen to agree. Wanted to clarify that since you mentioned it in the same thread.

BTW never said anything positive about MJ smoking and haven't had a toke in close to 35 years.  In fact, I posted a number of articles some time ago that stated MJ can accerlerate fibrosis. This is different however, from the use of medically prescribed marijuana during tx for nausea and wasting. I'm not promoting it, but do believe that nothing should be discounted to help someone stay on treatment when under a doctor's supervision.

Not picking any fights (your words), just trying to clarify.

Be well,

-- Jim

[amicraxy]

what ?????????????

[amicraxy]

the what goes dorfi

[jmjm530]

Here's a study 5 years out.

"...This study was reported at the AASLD conference just completed and shows from putting together from numerous Pegasys/Copegus studies that >99% of patients with SVR have maintained SVR for up to 5 years, as long as study has followed these patients so far..."

Full abstract here: http://www.natap.org/2004/AASLD/aasld_20.htm  If you do some more searching, you can find other studies longer out.

Also, go the clinical options website and watch the slide presentation by Dr. Shiffman. I believe he discusses this topic. If not there, check out the video presentation by Dieterich and Jensen on same site.

http://www.clinicaloptions.com/Hepatitis.aspx

[scubadiver30]

where are you going with this? you only search for papers that have bad or gloomy outcomes? You really want to get us down right? have you ever thought of reinfection? or old protocols that involved IFN standalone withou RIBA. Or simple medical bias? Or plenty of variables not covered in the current SOC?
Maybe those ex-patients in the research could not or would not kick their habits and continue IVDU after TX? or maybe they had other comorbid ilnesses underlying that made them require transfussions or IV medications that could also be tainted with HCV? It wouldn't be the first time that happens (specially in Spain) Rememeber dr Maeso?. In fact, you're pointing to some papers written by some of my doc's former students in Madrid. And my doc tells me that once a person achieves SVR can be considered cured. They will die for sure, but from something else, and maybe 40 years afterwards...
So I wonder if we're talking real facts or are we analyzing the ramblings of doctors that wanna get published in the Lancet no matter what...
I do believe in the healing power of mind and logic, and believe me, I'm not in denial.... I'll bring a copy of these to my doctor to see what he says about it.
I'll post his answers
regards
scuba

[drofi]

I think exactly the sanme as you do!!!! There are indeed good arguments that this tiny RNA in some cells has nothing to do with clnical outcome: The best evidnce is, that there are examples of people with SVR who had to get a strong medical suppression of the immune system and did not relapse, the just stayed Hepc free.
So, why I want those papers and good scientific links is just as a helping argument exactly for this opinion.
Sorry, I am not a native speaker, but hope you could understand what I mean.

Drofi

jmjm83: Your first link was nice, the second did not work, perhaps I could not search the side well, because of language problems. Could you help nme again, are the more facts similar to your first link?

[amicraxy]

As I am sitting here watching private ryan and crying over, weel you'd really have to be in my head instead of me trying to explain. Mind altering.  I have been alter with these drugs. For me that is very hard. I mean I can understand it and except it, but to really belive that I have not been able to nor do I seem to be able to put it aside, is harder.
I have been drug free in evry form for 18 yrs. and this is the first time I have been altered un naturaly.
I have said maybe 1000 times on tx  "What is wrong with me" or "What is happening to me"  intelectually knowing the answer but unable to realy belive it.  Maybe thats another sx of tx, an un easiness that creats denial

[merlino]

Please excuse me while I vent. I have had a morning from He&& trying to understand all this Hep c meds, resuce drugs, stay sane and so on and people actually come here and make believe they have Hep C!! Dear God, why????

[amicraxy]

I don't think there's any understanding during tx. Just know your not alone

[willing]

Here's yet another recent study supporting the durability of SVR <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16441471&query_hl=5&itool=pubmed_DocSum">Formann'06</a>.

As best I can tell, the following two observations are currently uncontradicted in peer-reviewed publications :

1) If you look for HCV RNA in serum via conventional commercial tests (eg COBAS Amplicor,Bayer/TMA etc) and don't find it 3 months post-tx chances are very good (high 90%s) you won't find it again.

2) if you go looking *inside* cells (pbmcs, liver) and use more sensitive detection protocols you do find it, often but not always and regardless of SVR status.

If anyone knows of published data contradicting either of the above please post!

[Oreos]

Cuteous!  Long time no see.  Thanks for the sane post. I hope you are well!

Drofi,
I'm 2 years post tx (1A 48/48 Peg/Copeg) and still undetectable.  Were the lingering effects of the meds worth it?  You bet.  Are there conflicting studies out there?  Of course.  You can drive yourself nuts worrying about relapse percentages. Definitely read the links from Cuteous...

[jmjm530]

Sorry. Should have mentioned that free registration is required for site. You should be able to register here:
http://www.clinicaloptions.com

---------------
Regarding studies you posted. You also might be interested in this in regard to "persistent" virus after SVR. The abstract references another study AASLD presentation LB9, the conclusion of which follows former abstract.

From: http://tinyurl.com/ydpcvu

"...The meaning of the detection of low viral load in patients after antiviral therapy for chronic hepatitis C with the new highly sensitive methods is controversial. It may be associated with a mild course of liver inflammation in single cases, but in most patients it does not show to have a clinical implication. Bigger and longer-term studies of patient cohorts after treatment should evaluate the meaning of low persisting viraemia.
Our data are in line with the abstract presented by Maylin et al (LB9, AASDL 2006) showing that SVR is associated with HCV eradication..."

From abstract LB9

CONCLUSION In our 345 patients with chronic hepatitis C and SVR, evaluated up to 18 years after treatment cessation, none demonstrated late relapse. In the 213 in whom liver tissues and/or PBMCs were available, 3 (1%) patients were detected HCV-RNA positive, by a very sensitive assay [TMA), in PBMCs (1 patient) or in the liver (2 patients). These results demonstrate a durable response to antiviral therapy with a marked improvement in liver fibrosis and indicate that SVR is associated with HCV eradication.

[Kalio1]

The way I understand it, "occult" virus does not contain replicating particles, so it isn't causing any harm even if they can find it.  It does not affect your SVR if you attain that status. It isn't like someone who  relapses who is undetectable on tx but when tx stops they still have replicating virus.

Like you say, you'd have to be reinfected to have the virus "come back" once you are SVR from tx for 6 months.
There is a less than 1% chance of it coming back.

[jmjm530]

OCCULT refers to individuals with non-detectible HCV RNA virus and showing no HCV antibodies who show virus in other compartments such as liver tissue. These individuals have NOT been treated. This has nothing to do with SVR.

PERSISTENT is similar but refers to individuals who HAVE been treated and achieved SVR. They have non-detectible virus but unlike with occult, they have antibodies.

[jmjm530]

Yes, an academic distinction, but as long as people are using these terms they mine as well be used correctly, especially since an "occult" study may not apply to SVRs.

You said: Will there be any viral copies somewhere in the body after SVR (as it is called today)and will these copies be able to harm liver and life.

As stated, that's controversial, especiall the latter part "will these copies be able to harm liver and life." Didn't read the Spanish study yet but all the studies I read suggest that the clinical signifiance isn't known, i.e. no statments that persistent virus will"be able to harm liver and life".

[cuteus]

http://www.natap.org/2005/HCV/010505_02.htm

while we are at the durability of SVR subject yet again.

[jmjm530]

Let me try and add to the list:

(3) It has not been established that there is any clinical significance to either "occult" or "persistent" virus.

(4) The reliability of some of these "more sensitive detection protocols" has not been established to the satisfaction of some doctors and researchers.

[drofi]

Thank you, I agree with your comments about differences between occult and persistency, but that is an academic discussion abou wording only. What is important is the question, will there be any viral copies somewhere in the body after SVR (as it is called today)and will these copies be able to harm liver and life. This is what the spanish group suggests.
Thank you for the new link, very good additional argument against the spanish suggestion!

Drofi

[DoubleDose]

I am enjoying the questions being raised on this thread, and enjoying the fact that I am not the one raising the questions.  At this point, I won't repeat my opinions, but merely state that there is much more to understand about this virus, and as time goes on we are going to find out many new things....both about the virus, its modes of infection, and the treatment, its impact and after-effects, etc.  The medical community often makes the mistake of trying to simplify something that is very complex.
As time goes by, the complexities unravel, overshadowing all the earlier simplistic thinking.  HCV may just be one of the bigger cases of this phenomenon.

I am taking the approach of not worrying about these issues for awhile, even though I know that many of the answers that will ultimately emerge will be pretty disturbing.   If that makes any sense.

I hope all of you are doing well!!!  

DoubleDose

[anise]

I really enjoyed this email discussion.  Many of the points raised have been on my mind.  BTW (somewhat off topic), many women are now beating breast cancer, as are other cancer patients, using chemicals.  I can  only hope that using chemicals, (which I never believed in the first place), will have a positive effect on Hep C in the long run.

revenire, I have to ask why you have this love/hate relationship with Kalio.  Is there something on your mind you might want to discuss?  You seem to be a very intelligent person, and I haven't seen you 'rail' against anyone else this intensely. Just curious why.

[drofi]

Your citation (Foremann) is confusing. They did not find any HCV, but was the test sensitive, they used the Cobas amplicor? What if the patients would be re-tested with a better test, see below?

Drofi

Here are some lines from a fromer link of this thread. Could someone help me to understand the difference?

"Consequently we tested sera of 50 patients with chronic hepatitis C  infection after treatment with PEG-IFNa + Ribavirin between 2001 and 2004.
All patients had a Sustained Virological Response (HCV-RNA negative by Cobas amplicorTM six months after therapy end). Sera at least 6 months after the end of treatment, stored at -20

[desrt]

Most of what I've read about finding HCV RNA after sustained response speaks of RNA fragments in specialized (compartmentalized) systems - i.e. cerebrospinal, lymph, etc. - suggesting whatever change the virus had to make to get into these systems has it trapped. As for the studies that found HCV RNA in the livers of SVRs, that's another matter.

[drofi]

where did you read that? Why are you sure the virus is trapped? To share opinions about these important points without a minimum of evidence does not have more value than an advertising in a newspaper of north korea.
I am not looking for more opinions, I have several opinions and can go to MacDonalds to collect some more, I am looking for good data or links and citations.
Drofi

[anise]

Thanks for trying to explain.  I still don't get it :)  However, you have a very poetic style to your writing.

[ladybug52]

POETIC?? I have to say that there is nothing poetic about arguing or putting others down. Rev I have to be honest- since this is your most obvious personality trait- you seem shallow, influenced by external beauty and self-righteous. Why do you think your biting sarcasm is welcome or appropriate? You  obviously are a miserable human being who does not make mistakes like us common folks and you really enjoy telling others how much they irritate you. I'm glad you have a forum to display your views--how lonely and miserable you would be without it.. Feel free to correct my spelling or judgement of you, I know this will add fuel to your out of control fire but I can't stand bullies.

[Kalio1]

"Flaming is the act of sending or posting messages that are deliberately hostile and insulting, usually in the social context of a discussion board on the Internet. Flaming is said by some to be one of a class of economic problems known as The Tragedy of the Commons, when a group holds a resource (in this case, communal attention), but each of the individual members has an incentive to overuse it. Flamers usually call their flames justified attacks.

Although the trading of insults is as old as human speech, flaming on the Internet, like many other online 'actions', started in the Usenet hierarchies. A flame may have elements of a normal message, but is distinguished by its intent. A flame is typically not intended to be constructive, to further clarify a discussion, or to persuade other people. The motive for flaming is often not dialectic, but rather social or psychological. Sometimes, flamers are attempting to assert their authority, or establish a position of superiority. Other times, the flamer is simply closed-minded or biased, and is simply shocked and appaled that anybody would dare to have an opinion that isn't the same as that of the flamer, so he/she personally attacks the "dissenter." Occasionally, flamers wish to upset and offend other members of the forum, in which case they are trolls."

[agathis]

good lord, you guys to love to hear yourselves talk. and the later in the evening it gets the more verbose you are.
this is my first time to the site, i had 24 weeks of peg/interferon in 2001, am a sustained responder - for now-
my question to you guys- have you heard of anyone having a skin condition known as granuloma annulare as a result of treatment?
i have had it for 3 yrs now, and it continues to spread.

[Kalio1]

Welcome to the forum. Hope you can just ignore some of the more inappropriate comments and focus on the helpful ones.

Sorry to hear you are dealing with this, the only thing I could find on it said it is sometimes occurs in those with Diabetes or people with thyroid issues. Hav ou had our thyroid checked? Both HCV an treatment are known to affect your thyroid.

Hope you find a solution, that sounds hard to deal with.

[beamishboy]

REV- say it ain't so!!..puff,puff..pot "destroys liver" ??..puff,puff..~(-:/......skip gitmo and go directly to havana.....everything is cheaper & the music is much better
kalio- i thot flaming was  very 'out' behavior of certain persuasions..such as priscilla of the desert waltzing down the 'commons' path ,strutting herstuff.....out,proud & in your face.....isn't that a bettr image ?.....(-:

[Kalio1]

Both definitions seem to apply here.
I can see him all dolled up in makeup and heels typing feverishly away from his little troll cave.

So how's post tx? Seen any improvement? It seems the improvement isn't immediate, but I hope you are feeling good.
Im soo sick of this **** but I am encouraged by the results of the election.