SVR Eradicates HCV

[mremeet]

Not sure if this has already been posted, if so it bears repeating:

http://www.natap.org/2008/EASL/EASL_77.htm

"SVR Eradicates HCV

SUSTAINED VIROLOGICAL RESPONSE IS ASSOCIATED WITH ERADICATION OF HEPATITIS C VIRUS AND DECREASE IN ANTI-HCV TITER IN PATIENTS TREATED FOR CHRONIC HEPATITIS C

Reported by Jules Levin
43rd Annual Meeting of the European Association for the Study of the Liver April 23-27, 2008, Milan, Italy

M. Martinot-Peignoux1, S. Maylin1, N. Boyer2, A.C. Cardoso1, M.P. Ripault2, N. Giuily2, C. Castelnau2, M. Pouteau2, P. Bedossa3, P. Marcellin1,2 1 INSERM, U-773, Centre de Recherche Biomedicale Bichat-Beaujon CRB3 Hopital Beaujon, Clichy, 2 Service D'Hepatologie, Hopital Beaujon, Clichy, 3 Service D'Anatomie Pathologique, France

ABSTRACT

Background-Aim: Hepatitis C virus (HCV) eradication, in patients with chronic hepatitis C who achieve a sustained virological response (SVR), is still controversial. In this study performed in patients with chronic hepatitis C who achieved an SVR, HCV-RNA was measured in serum, peripheral blood mononuclear cells (PBMCs), liver and anti-HCV antibodies titers were assessed, during follow-up.

Methods: 278 patients with an SVR after treatment with IFN alpha-2b or PEG-IFN alpha-2b+ribavirin, were studied. HCV-RNA was tested: in serum for all the 278 patients every year and at the time of PBMCs or liver collection; in PBMCs in 71 patients 3.9±3.4 (0.5-10) years after treatment; in liver 38 patients 3.2±1.6 (1-5) years after treatment. HCV-RNA was detected with the VERSANT HCV-RNA Qualitative assay (TMA). In 142 patients HCV antibody titers were measured with the Axsym HCV 3.0 (Abbott), and with the third-generation HCV recombinant immunoblot assay (RIBA) (CHIRON RIBA HCV 3.0 SIA), before therapy and 4.7±2.2 (0.5 to 11) years after treatment. Liver histology was assessed in 92 patients with paired biopsies 1.4±1.9 (0 to 10) years.

Results:

Patients were followed up for a mean of 3.5±2.4 years (range, 0.5-17) years.

Serum HCV-RNA remained undetectable in all the patients (1050 samples).

None of the patients had detectable HCV RNA in the PBMCs or in liver.

The mean anti-HCV titers were 93±19 IU/ml and 45±21 IU/ml, before therapy and on the last serum sample available, respectively (p < 0001).

The most significant decrease was observed with anti-NS5 antibodies (p = 0.001); anti-c22 antibodies remained unchanged.

Normal serum ALT levels were maintained in 94%, fibrosis stage was improved in 57%, stable in 32%, deteriorated in 11% of the patients.

Regression of cirrhosis was observed in 7 of 10 patients.

Conclusion:

In our 278 patients with chronic hepatitis C and SVR, evaluated up to 17 years after treatment cessation, none demonstrated late relapse or the presence of HCV RNA in serum, PBMCs or liver.

HCV antibody titers showed a marked decrease. These results demonstrate a durable response to IFN alpha 2b or PEG-IFN alpha-2b+ribavirin and indicate that SVR is associated with HCV eradication and progressive decrease of anti-HCV."

[willing]

>my specialist works at the main pond
no matter how good you are, it's hard to be in two places at the same time. If you're seeing patients, you're not at the bench, no doubt part of the reason pathologists are so hard to reach. Next time you  see him, you might ask when was the last time he picked up a pipetman.

>make you stubborn as a mule
I suppose I should be grateful it's not a horse joke, but yes, I've already been warned in that regard... and thanks for the h pylori tip!

[mikesimon]

My surgeon thought it was HCV before even seeing my biopsy report - just by seeing the enzyme history.

I really don't know what to think about me and HCV. I can tell you that I was really surprised when the chief pathologist gave me the story. I just wanted to know the specific molecular test that showed HCV. I was floored when he told me there was no test. If I gave you the pathologist's name and you Googled him you would be amazed at how much he publishes and the complexity of topics he addresses. This man is one of the preeminent pathologists in the country so when he told me that "negative serum HCV RNA testing does not mean that the liver tissue is negative for HCV" I have to believe that he has seen it in his lab on more than one occasion.

To be clear about this I never asked my surgeon this specific question. I haven't even seen him since the biopsy results so I cannot say that he intentionally or negligently misled me. Maybe hes seen so many serum undetectable patients show HCV on biopsy that he just accepted the results as accurate. When I first posted the story about my biopsy Jim and willing wanted to know what test was used and I started investigating. When I saw the disclaimer regarding molecular tests which were not FDA approved but were developed at my center I figured that one of the listed tests was the one that was used. At the time willing and I were in touch with one another and it was willing who called my attention to the fact that immunochemistry-based detection of HCV proteins in biopsy samples is possible and that the language on my biopsy report contained references to those types of tests. That's what I thought the pathologist was going to tell me - which specific test was used. Suffice it to say that I am not happy about this. Since I have been serum undetectable since 2003 and stopped TX in June 2004 I think a PCR of my liver tissue in June 2006 would have been more than reasonable - it should have been mandatory. My surgeon was out of the country when the biopsy was ordered so I can't necessarily blame him for the order although I don't completely absolve him of responsibility either. But after he saw the results he should have sent me immediately to get another biopsy with a tissue PCR to be certain about what was causing my enzyme elevation. There's nothing to biopsies as far as I'm concerned  - except the results that is. I really don't know exactly how many I've had because I have had a bunch. And they sure aren't anything to the surgeons - they order them all of the time at the drop of a hat. I think a PCR should have been done on my tissue without question. The fact that it wasn't does trouble. I am reminded of what my surgeon told me just 2 or 3 days after my transplant. He said "don't trust anyone" and I replied "except you, right?" and he said "no, not even me". It does seem that the older I get and the longer the relationship the greater the likelihood of disappointment. If I have learned anything through this is that my surgeon was right when he told me not to trust anyone. And the mistake I made was to trust. When my AR dose was being reduced (it was a weaning off process of all AR drugs) I thought that the reduction that triggered my problems was too drastic. I also thought that testing every two weeks following the dose reduction was not frequent enough. I thought I should be tested every week.  I did question the 2 week testing interval but I finally acquiesced to it because I trusted my team despite the fact that it just didn't seem like the prudent course. I will try very hard never to make that mistake again. I believed that I was too seasoned a patient to allow something like this to happen to me. And, I know that I am far more experienced than most patients and I cringe when I think of what other less experienced and less knowledgeable patients might permit and acquiesce to. It's a jungle out there and particularly so when you're sick.

Maybe ignorance is bliss in my case but I always do like to know what the real facts are - even if they aren't encouraging or favorable

Mike

[jmjm530]

Willing:...l ike Jim's specialist, who work further downstream (for many Dr's, the personal definition of cured probably comes down to the fact that they never see SVR patients again).
---------------
Actually my specialist works at the main pond and I'm still seeing him two years after SVR. Do watch out for those oats btw, they can make you stubborn as a mule :)

[willing]

CS : thanks for the explanation; yes, given that the study is reporting results on patients who had never undergone tx,  SOC protocols seem irrelevant to the findings

all: interesting twist in a various ways : the assumption that the inflammation is HCV-related and the pathologists' comments, however,  on a personal note, it's got to be good news!

The discrepancies between what reputable specialists have to say on the topic underscores for me that the issue is still very unsettled, hence the ongoing controversy  on this forum and in the published literature is not idle bickering.

Personally I tend to give more credibility to those working at the lab-bench/microscope, like Mike's pathologist, than to clinicians, like Jim's specialist, who work further downstream (for many Dr's, the personal definition of cured probably comes down to the fact that they never see SVR patients again).

[DoubleDose]

Your comments are really good news, especially from your personal perspective.  In the few studies that I have read regarding positive hepatic virus and negative serum virus, after treatment, I do believe that the LFT's were somewhat abnormal in the liver positives.  I can't imagine that with LFT's consistently in the teens that you would have active or chronic virus in the liver.  You sure have a great shot at good news, anyway, since you had no PCR of tissue, and now understand that there was no confirmation of active virus other than some circumstantial inflammatory signs in the liver tissue.  I would think that to be probably typical.

I do think that the issue of persistence probably is a little different from the issue of positive/ or negative hepatic tissues after SVR, in that I would think the persistent viral matter would be sub-detectable (if there is any actually there), and would need extreme amplification to detect.  It would likely be in various other organs and tissues as well.  The real question ends up being one of 'accurate PCR test results with true low level replication, vs. some other manifestation or contamination that shows up as 'replicating virus' on extreme PCR amplification.  I am uncertain if either position has much certainty at this point, which is why I remain open to final determination by scientists.  Although some of us are said to be in the 'viral persistence' camp, I would characterize it as the 'open to the concept of viral persistence, as research has frequently suggested' camp.  At the same time I sense that others are in the 'absolutely sure it is eradicated, and totally cured' camp.  That is just fine with me, and it is their right to hold that opinion.  In fact, I really hope that they are right!

I think the issue of liver infection, with a positive PCR using ordinary testing is another subject apart from 'persistence' and may be related in many ways, or more similar to Occult HCV, or they may all be manifestations of the same thing, just moving on a continuum from very invisible to very obvious.  

I hope that when and if you do the biopsy/ PCR that you end up seeing only a big goose egg!!!  I think you will!  

Thanks for the candid retraction and clarification...it puts everything in a much nicer light for you, and for us!  Your surgeon does seem to see the possibilities for different viral outcomes, and SVR behaviors, and that in itself is another red flag waving toward the need to further study 'occult', AND 'persistent' HCV.  I believe this, anyway.

DoubleDose

[mikesimon]

No - and I was tested 1 or 2 weeks before and 10 days or 2 weeks after. I would have to check to be precise about the time but both the before and after were absolutely positively within one moth of my biopsy.

Yes, there was no PCR or molecular testing of the tissue sample so that question is up in the air - whether there is any active HCV in my liver.

I don't know when I want another biopsy. It's not the procedure that scares me - it's the results. My enzymes have been consistently in the low teens since they normalized and I get a whole lot of labs - every two weeks. So I think I have a clue about my liver healthy without a biopsy.
But, when I do get one you can be sure the tissue sample with undergo PCR testing - without question.

All is well on this end and I hope that you and your family are well also.

Mike