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."

[mikesimon]

I was HCV positive prior to transplant. I was transplanted in June 2000 and I was diagnosed in January 1995 after a major variceal bleed.
I received an HCV negative liver. I saw that pathology report.
I treated within 2 months with regular interferon 3 x per week and low dose ribabvirin for 1 year. I didn't clear.
6 months after stopping my first treatment I retreated with standard dose Peg-Intron standard dose and low dose ribavirin for 53 weeks. I cleared late and relapsed immediately.
I treated a third time within 3 weeks of my second treatment. I treated for 73 weeks with standard dose Pegasys and weight based dose ribavirin. I cleared at week 12 or possibly week 11 and stopped in June 2004. I first tested undetectable in April 2003 and have never tested detectable since that time and I have tested every month since stopping in June 2004 with Heptimax <5 IU/ml.
I do not recall the particulars of the pathology report on my donor's liver. Since it was a cadaver liver I assume a PCR was performed on the tissue since no serum was probably available at my center. That is a good question though. I apologize for the fact that I will not investigate that issue. I've had enough of that stuff for a while.
Mike

[mremeet]

Thanks for the clarification on the biopsy PCR results. I don't recall your entire history, I know it has many twists and turns though (this being one of them). One thing I was curious about though: Did you have HCV prior to your transplant and managed to SVR shortly thereafter? (via SOC) Or you did have HCV but managed to SVR just prior to your transplant? I can't remember what exactly happened. And the thing I'm wondering about, is that since people who have HCV (or test + for HCV antibodies) can and do donate livers upon their death - and considering that you would probably show up in the transplant recipient database as either having or had HCV, would that mean that you might (or would) get a liver from an HCV+ (or antibody +) person? Maybe you didn't and received a liver from a "clean" person never infected with HCV (SVR or otherwise). But considering the relatively close sequential timing of your treatment, SVR, and transplant combined with some possible bureaucratic chaos in how you may have been classified in the transplant database, I might be a bit concerned about the possibility of getting an infected liver, or perhaps a liver from an SVR which may have "persistent" virus in it.

But maybe not and you know for an absolute fact that your new liver was clean - just a thought I was curious about that may play into the whole confusion. I also wonder how new livers that become available for transplant are screened prior to transplant. Do they perfrom a PCR for HCV on them? Or simply measure for HCV antibodies? Or....???

[mikesimon]

Well we agree on that. I wouldn't have had a biopsy if I didn't have a problem. And that's why I won't run out and get one now. I don't mind them that much but it's not my favorite way to spend an afternoon either. And, you're right. Regardless of the results I cannot do anything about it. The point is I had the biopsy because my enzymes were elevating and I was also an SVR. Let's agree that a PCR of my tissue should have been done. If it ruled out HCV then it would have been far more likely that I was experiencing "some minor component of rejection" as the chief pathologist put it. And that would have been useful to know for many reasons not the least of which is to shed light on my chances to wean myself off of all the AR meds. Mike

[jmjm530]

As stated in probably what were crossed posts, I do agree with your decision and might do same in your shoes. But no, personally, I would not do it for myself for reasons originally stated nor in fact would I have another biopsy unless the docs felt my liver was acting up.

[jmjm530]

Our posts probably crossed but that's pretty much what I said in my last post to Mike.

[mikesimon]

Well Jim, I'm not running to get a biopsy so it's not an urgent matter. I am only saying that if I got another biopsy I would definitely insist that the tissue be tested for HCV. If you were to have a biopsy wouldn't you want the tissue tested? I think most of us would like to know as much as we can even if there isn't anything we can really do about it.
I want to know this stuff and what better place to learn than my own liver - particularly with my history. I would have thought my surgeon would have wanted to know for certain whether HCV was active in my liver. Looking back I think I was rejecting and it was as simple as that. Distinguishing acute rejection from HCV on biopsy is very difficult because they look the same. So how could the pathologist have known what was causing my inflammation and fibrosis? All the pathologist had before him was my age, my underlying disease and the date of my transplant. So he called it HCV. Perhaps if he had in front of him my serum undetectable tests since April of 2003 and my recent AR dose reduction he might have called it acute cellular rejection. I think that would have fit just as well as HCV.  
Basically we get a biopsy to learn about the state of our liver. A PCR of the tissue just adds to that information so it should have been done without question.
Mike