remission

[mikayla3]

has anyone been hep-c remission and had it return after years?

[HCA]

Onlly by reinfection.
Relapse post 24 weeks SVR is vanishingly rare.

[YuK]

If or I should say WHEN I get to post 24 wks, I'm going to celebrate with a nice glass of wine.

[copyman]

when you say "remission" do you mean someone that has treated & SVR'd or the virus went away on its own (immune sys fighting it off)? If someone treated successfully and are virus free after one year then chances are almost nil. Unless by reinfection like the other poster said.

[franke566]

I finished treatment nearly 4 years ago and my last two viral loads tested positive.  I am taking the advice of jmjm and going to have a Hepatimax test drawn next week, Franke566 to rule out a false positive or the test was not the right one in both cases.  Thanks jmjm

[portann]

If you had HCV and treated successfully so that no HCV RNA was detectable in your blood stream for six months after treatment (some say one year) , then you're considered SVR or cured. You will always test positive for HCV antibodies.

If you test positive for HCV RNA via PCR or TMA viral load testing down the road, it's because you were re-infected, not relapsed.

Unfortunately, clearing the virus provides zero protection from contracting it again, either the same or different genotype.

There is ongoing discussion here about 'occult' hepatitis, that is, some residual HCV that remains even when SVR. From what I understand,  this may be the case but it doesn't have any replicative ability or clinical significance.

[Mr Liver]

SVR is not ironclad at 6 months undetectable. I know some believe it is supposed to be but the drugmakers claim no such thing and the trials and studies confirm this fact. SVR rate is 97% tops after 6 months undetectable. This means an avg of 3 ppl out of 100 ppl will relapse beyond the 6 month eot test. Real people are behind those numbers. I am sure more than one person has passed through here with tales of late relapse ( a year or 2 post 'svr' ) that could in all probability be part of this 3%.

3% doesn't sound very large and in truth it's not in most scenarios. An airline company that has a 3% crash rate would not last too long in business, however. It's all a matter of perspective.
ML

[portann]

I wonder then if that view holds that the SVR rate at six months is 97%, what is that view's position on the twelve month or two year?

[apache1]

Well, Mr Liver, you might need a little GREY POUPON for this study...lol
not one from this large study relapsed. 3.27median years after SVR. was100% durable....
http://www.hivandhepatitis.com/hep_c/news/2008/101408_a.html

As reported in the September 2008 issue of Gastroenterology, French researchers conducted a long-term follow-up study of 344 chronic hepatitis C patients who achieved SVR with interferon-based therapy. Participants were followed for a median of 3.27 years (range 0.50-18 years).

The investigators looked for the presence of residual HCV RNA in blood serum, liver, and peripheral blood mononuclear cells (PBMCs) using transcription-mediated amplification with a sensitivity of < 9.6 IU/mL. In addition, they evaluated liver fibrosis progression in biopsy samples according to the METAVIR scale. A total of 114 patients had post-treatment liver tissue assessments and 156 had PBMC assessments.

Results

    • Serum HCV RNA remained undetectable in 1300 total samples.

    ***• None of the patients experienced HCV relapse according to serum measurements.***

    • HCV RNA was also not detected in any of the 156 PBMC specimens.

    • However, HCV RNA was detectable in 2 of 114 liver specimens (1.7%).

    • Histological analysis of 126 paired pre- and post-treatment liver biopsy samples (median 0.50 years apart) showed that fibrosis stage improved in 56%, remained stable in 32%, and worsened in 12%.

    • Regression of cirrhosis was observed in 9 of 14 patients (64%).

    • No cases of decompensated cirrhosis were observed.

    • 3 patients developed hepatocellular carcinoma.

"In this large cohort of chronic hepatitis C patients, SVR was durable up to 18 years after treatment cessation, in addition to fibrosis stability/improvement (88%) and cirrhosis regression (64%)," the researchers concluded.

"The presence of residual HCV RNA was observed only in liver tissue (1.7%)," they added. "This result strongly suggests that SVR may be considered to show eradication of HCV infection."

Université Paris VII, Hôpital Beaujon, Clichy, France; Service de Microbiologie, Hôpital Beaujon, Clichy, France; INSERM U-773, Centre de Recherche Biomédicale Bichat-Beaujon CRB3, Hôpital Beaujon, Clichy, France.




Here is another study, it is not nearly as good results...only shows 99% durability after 5 years, oh well.

http://www.hivandhepatitis.com/2008icr/ddw/pdf/LTFUFinal.pd.pdf

Here is another study here that shows 99.6% from a study with 987 long term follow up of up to 13 years

http://www.hivandhepatitis.com/2008icr/ddw/pdf/LTFUFinal.pd.pdf

Some of these studies suggest the small amount of relapser's might be in some part re-infections. Actually I am surprised there were not a considerable amount of relapser's that went back to their old ways, and got reinfected.

SVR is durable, and approaches 99 - 100% in studies I have read.

apache

[Mr Liver]

Thanks for your reply, but I would hold onto the mustard. ;)

As noted there were 4 relapsers identified in the first study.


“Methods: 567/1695 (33%) subjects from 2 clinical trials (Lindsay et al, Hepatology 2001;34:395-403; Manns et al, Lancet 2001;358:958-965) who were treated with PEG±riba and completed 24 weeks of follow-up were assessed annually for up to 5 years for clinical evidence of liver disease progression and virologic evidence of relapse.”

Out of the 1695 who attained SVR,  38% (644 people) were SVR via IFN monotherapy. It can easily be argued that including those in the study results could skew the final outcome. Monotherapy treatment has a 10%-15% SVR rate for the old 3X a week IFN with slightly higher rates for peg monotherapy.  A stronger innate immune response is a predictor of SVR as you probably know. To clear HCV with IFN monotherapy suggests a more robust innate immune response in those individuals and fewer relapsers would be one result of this. This is not considered in the study.

And finally, the sensitivity of the 6 mo post-tx  tests  upon initial enrollment in the original study had lower detection limits of <125 and <50 which could result in the failure to detect 100% of the relapsers upon the 6 month EOT test.

This is from the McHutchison paper cited by the above study:

“Probability of SVR for the 5-Year Post-Treatment Follow-Up
• Kaplan-Meier estimate of continued SVR over 5 years was
99% (95% CI: 98%, 100%) (Figure 2) based on the
5 definitive relapsers  
— The estimate was 97% (95% CI: 95%, 98%) if the 7 possible
relapsers were included in the calculations. “

In his paper the detection limit was:
“Assessments
• Measures of hematology, biochemistry, gastrointestinal/liver examination, and quantification of HCV RNA by polymerase chain reaction
(PCR) with sensitivity of 100 copies/ml (National Genetics Institute) and after March 2001 by TaqMan (Schering-Plough: sensitivity of
29 IU/ml) were performed yearly during the 5-year post-treatment follow-up”

He concluded: “ Patients treated with interferon alfa-2b with or without ribavirin who achieve SVR have a 97% to 99% probability of remaining virus
free 5 years later.”

One can logically assume that the further from the 6 mo post-tx test the durability of SVR increases. Those with SVR at 6 months post-treatment had a 97% chance of remaining virus free.

I have always contended that SVR is quite durable. I have never seen a case of relapse beyond 3 years that could be proved conclusively. I believe we were both in a thread recently where I took this position. But, 97% is not 100% and that was my point. SVR is not durable 100% at 6 mo eot test. Over the years I have known many people who have relapsed after their 6 mo post-tx PCR. Some I’m sure relapsed before the 6 month or 1 yr post-tx PCR but were not detected due to testing limitations at the time. The very same problem that bedevils the studies you cited. Thanks again for your reply and the studies cited.
ML

[jmjm530]

SVR is not durable 100% at 6 mo eot test.
----------------
My understanding is that SVR is durable somewhere around 98% at the six month mark but does approach 100% at the 1 year mark. Beyond that, and perhaps even within that time frame, one has to consider re-infection as a cause for any positive virus tests.

-- Jim

[Rockerforlife]

Im scared to death to get my teeth cleaned now....before i dod again i want to see how they clean the instruments and the all the equipment...and that suction hose they stick in your mouth...how clean is that hose that takes out the gunk?...does it back wash?

[portann]

Portann:  "If you had HCV and treated successfully so that no HCV RNA was detectable in your blood stream for six months after treatment (some say one year) , then you're considered SVR or cured. You will always test positive for HCV antibodies."

So then how would you correctly re-state the above, based on your statements?

   "If you had HCV and treated successfully so that no HCV RNA was detectable in your blood stream for six months after treatment (some say one year) , then 97 -98 % of you are considered SVR or cured. You will always test positive for HCV antibodies."

Thanks for the input.

[Rockerforlife]

http://www.ada.org.au/App_CmsLib/Media/Lib/0612/M43672_v1_633020326645646250.pdf

[apache1]

Mr Liver,
Looks like we both have studies to back up our numbers.

In reality we are both right. There will always be some relapses. Are they re-infections? maybe some. Are some actual SVR relapses, probably. Is it 0 in 100... but 7 in 1000 ? maybe. Did older studies use now outdated VL test that did not spot relapses before the 6mo mark ? maybe.
Would new studies with new sensitive vl testing prove SVR more durable?... I think we will see that in the future


Its all in the semantics.
99% is not aceptable in your airline analogy.
99% is attractive, very acceptable odds at the Hard Rock tables any nite.

If I am lucky enough to make it another 29 days still und at my 6 month post eot. I will gratefully accept those 100% - 97% odds for SVR durability.

I know not much in this world is 100% or even 97%.
But somewhere in there its about as good as it gets for us.

apache

[annieCinMD]

There is a member of this forum (not a very active poster) who treated and cleared 10 or more years ago, and relapsed. I don't want to bust out their anonymity, but from what I know about this person, it is probably not a reinfection. They are treating for the second time right now. A very unusual situation, but it can happen. The odds are probably akin to sexual transmission, possible but highly improbable. Just a hair to the left side of a standard Bell curve with Impossible being on the extreme left and Certain being the extreme right.

[newleaf09]

I've come across references in the literature (naturally I can't remember where now) about medications or ailments that suppress the immune system.  Treatment is said to leave us with such a hyped up immune system that any leftover HCV genomic material can never replicate again.  Perhaps if you take meds that suppress the immune system, that can allow the virus to begin replicating again.  Previous mentions of this thought have caused controversy on this forum.

[Rockerforlife]

I still think dentists are the culprit of the" remission issue"...i do not trust them at all

[willing]

annie: I've often wondered why no-one in that category had shown up on this forum; if they were motivated to share particulars of their tx (probaly mono?) /relapse/vl testing I'm sure it would be of general interest (though I can easy see why one might not want to go through that; this topic always seems an emotional one )

ML: mustard or not, it's amusing to see you arguing both sides of this in different threads on the same page.. re : "I have never seen a case of relapse beyond 3 years that could be proved conclusively." it's hard to see why 2.5 or 5 year relapses are any more conclusive. Short of pre and post tx sequence data it's pretty much impossible to distinguish relapse/re-infection. The PI trials have been collecting a lot of that, and if any late relapseses occur among those SVRs there will finally be something close to proof.

However, the cases of relapse shortly after immune suppression, such as the 15 month post SVR liver transplant-recipient who relapsed a couple of months after steroid bolus injections as discussed earlier,  seems  harder to dismiss.

Apache:
Re 97 vs 98 vs 99.999999 that recent Zeuzem review
http://www.ncbi.nlm.nih.gov/pubmed/19105211
summarizes all published  data reported over the past 15 years or so and averaged  out the post SVR late relapse odds:

as detected in serum :  3% (table 2)
in serum among immune-compromised (primarily transplant recipients): 2% (table 3)
in liver cells 5% (table 4)

Of course averaging lots of unreliable data doesn't  improve its quality.
BTW if you understand the logic of  "residual HCV RNA was observed only in liver tissue (1.7%).. This result strongly suggests that SVR may be considered to show eradication"
please explain, that one always puzzled me.

also, there's a more recent Maylin'09 paper
http://www.ncbi.nlm.nih.gov/pubmed/19076273
that covers the same ground as the '08 one but you cited but includes the interesting twist that Abs for viral proteins other than core exhibit marked decrease in SVRs:

"A decrease in the antibodies against the NS3, NS4 and NS5 proteins, observed in our study, could reflect a decrease in infected cells, suggesting that there is no antigenic stimulation after viral eradication. Furthermore, NS3 and NS5 antibody titres have been reported to be markers for chronicity (26) with a rapid significant decrease after treatment-induced viral eradication or in immunocompetent patients with self-resolved infection. This finding is supported by our previous study (27) showing significantly lower HCV antibody titres in untreated patients with persistently normal ALT and without detectable serum HCV-RNA (absence of ongoing infection) compared with those with detectable serum HCV-RNA (ongoing infection). Furthermore, our data are supported by the study by Takaki et al. (14) reporting a gradual decrease and disappearance in the HCV-specific antibody after recovery from HCV infection. Evidently, humoral immune response to non-structural proteins is short lived and might be a marker of infected cells destruction."

mre has argued in the past that this is evidence for eradication at SVR; I tend to see it more as evidence that the residual virus keeps declining, possibly reaching eventual eradication.