Aa
SVR Eradicates HCV
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."
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."
sorry, but I didn't understand your comment. Both quotes in the preceding post are from recent articles. Ishii'08 is
Immune responses during acute and chronic infection with hepatitis C virus.
Clin Immunol. 2008 Aug;128(2):133-47. Epub 2008 Jun 2.
PMID: 18514579
and Hoare'08, the most recent addition to the 'occult hcv' health page, is
Histological changes in HCV antibody positive, HCV RNA negative subjects suggest persistent virus infection,
Hepatology, (still pre-print)
Immune responses during acute and chronic infection with hepatitis C virus.
Clin Immunol. 2008 Aug;128(2):133-47. Epub 2008 Jun 2.
PMID: 18514579
and Hoare'08, the most recent addition to the 'occult hcv' health page, is
Histological changes in HCV antibody positive, HCV RNA negative subjects suggest persistent virus infection,
Hepatology, (still pre-print)
Careful quoting that study. When i did further up the thread, the data was considered too old to be meaningful as it was before the Peg/Riba era.
Ok i thought he missed the point, but hey If he wants to believe that so be it.
CS
Ok i thought he missed the point, but hey If he wants to believe that so be it.
CS
DD:
thanks for the update; very glad to hear you're doing well. If you can handle long-distance flying and still feel well I'd say your health is way ahead of the median..
moahunter:
>If it is gone in a meaningful way, why is this research important?
(1) in-depth understanding of how hcv interacts with the immune system, even beyond SVR, is of value in vaccine development and in tx design for non-responders/relapsers (2) you learn a lot about how something is put together when it breaks; HCV breaks our immune response in fundamental ways, it has a lot to teach us.
mremeet:
>You fail to provide any information or evidence or data to >substantiate this improvement, nor do you explain how this >improvement process takes place in tx failures and SVR's,
if I'm understanding you correctly, you're questioning whether control of the virus could be due to an improvement in the immune response? But that's precisely what adaptive immunity is all about!
See the wikipedia article for an introduction:
http://en.wikipedia.org/wiki/Adaptive_immune_system
Development of strong HCV-specific, antigen presentation and CDC4+ CD8+ Tcells is the crux of immune control. From a recent review out of Harvard (yeah, I know, more ad-hominem name dropping)
http://www.ncbi.nlm.nih.gov/pubmed/18514579
"CD4+ T cells have multiple effector functions in antiviral responses,
both via secreting antiviral cytokines and via activating
viral specific B cells and CD8+ Tcells. A strong preponderence of
evidence demonstrates that in the acute phase of HCV infection,
vigorous, broadly directed and sustained HCV-specific
CD4+ and CD8+ Tcell are closely associated with a self-limited
course of infection [26,84–88]. HCV-specific T cell responses
and the induction of IFNγ in peripheral blood and liver coincide
with a decrease in HCV RNA titers [26,30,89], although there is
a notable lag between the onset of viremia and the onset of T
cell responses [26,89,90]"
A free-access overview is:
http://www.ncbi.nlm.nih.gov/pubmed/10790425
The 'strong preponderance' mentioned above is primarily in the context of acute; there's not yet as much data distinguishing successful vs failed tx on the basis of CD4/CD8 profiles but it seems a likely extension.
> nor (once again for the 4th time) did you address (in any way)
I did, it was buried in the 'etc.etc.' fine print regarding conjectures. Maybe the impregnability of SVR even in the face of immune-suppressive medication supports absence of viable virus; equally plausible is the conjecture that the suppression is nowhere near strong enough to cause resurgence (did you develop any major bacterial or viral infections while taking that 80mg of prednisone?). And again note that there *is* some, though scant, documented evidence of resurgence as posted above. However, there's not much point arguing about this - it simply isn't direct evidence, pro or con.
>your mind is made up and you believe in viral persistence
..
>only referencing studies that support your point of view
not so - as noted above, in addition to Maylin'08 there are two other recent studies that report no finding of post-SVR HCV RNA in PBMCs (and all three failed to apply mitogen stimulation of cells prior to PCR). The list of research TN has compiled on the 'occult' health page speaks for itself. If you believe it's one-sided you should extend it; I'll be surprised if TN has missed much.
And BTW, his most recent addition (Hoare'08, he now seems to be adding pre-prints even before publication! you'd think keeping that hair-do in shape wouldn't leave him much time) concludes with
"Non-viremic HCV-antibody positive patients have a liver biopsy that is usually abnormal. Fibrosis was present in most with similar inflammatory infiltrate to viremic cases. The presence of a CD8+T rich inflammatory infiltrate suggests an ongoing immune response in the liver, supporting the view that HCV may persist in the liver in the majority of HCV-RNA negative cases"
None of these patients had undergone tx, their HCV-RNA und status is due to their unaided immune respose. However, as I recall, you were arguing a while back that all SVRs are created equal..
thanks for the update; very glad to hear you're doing well. If you can handle long-distance flying and still feel well I'd say your health is way ahead of the median..
moahunter:
>If it is gone in a meaningful way, why is this research important?
(1) in-depth understanding of how hcv interacts with the immune system, even beyond SVR, is of value in vaccine development and in tx design for non-responders/relapsers (2) you learn a lot about how something is put together when it breaks; HCV breaks our immune response in fundamental ways, it has a lot to teach us.
mremeet:
>You fail to provide any information or evidence or data to >substantiate this improvement, nor do you explain how this >improvement process takes place in tx failures and SVR's,
if I'm understanding you correctly, you're questioning whether control of the virus could be due to an improvement in the immune response? But that's precisely what adaptive immunity is all about!
See the wikipedia article for an introduction:
http://en.wikipedia.org/wiki/Adaptive_immune_system
Development of strong HCV-specific, antigen presentation and CDC4+ CD8+ Tcells is the crux of immune control. From a recent review out of Harvard (yeah, I know, more ad-hominem name dropping)
http://www.ncbi.nlm.nih.gov/pubmed/18514579
"CD4+ T cells have multiple effector functions in antiviral responses,
both via secreting antiviral cytokines and via activating
viral specific B cells and CD8+ Tcells. A strong preponderence of
evidence demonstrates that in the acute phase of HCV infection,
vigorous, broadly directed and sustained HCV-specific
CD4+ and CD8+ Tcell are closely associated with a self-limited
course of infection [26,84–88]. HCV-specific T cell responses
and the induction of IFNγ in peripheral blood and liver coincide
with a decrease in HCV RNA titers [26,30,89], although there is
a notable lag between the onset of viremia and the onset of T
cell responses [26,89,90]"
A free-access overview is:
http://www.ncbi.nlm.nih.gov/pubmed/10790425
The 'strong preponderance' mentioned above is primarily in the context of acute; there's not yet as much data distinguishing successful vs failed tx on the basis of CD4/CD8 profiles but it seems a likely extension.
> nor (once again for the 4th time) did you address (in any way)
I did, it was buried in the 'etc.etc.' fine print regarding conjectures. Maybe the impregnability of SVR even in the face of immune-suppressive medication supports absence of viable virus; equally plausible is the conjecture that the suppression is nowhere near strong enough to cause resurgence (did you develop any major bacterial or viral infections while taking that 80mg of prednisone?). And again note that there *is* some, though scant, documented evidence of resurgence as posted above. However, there's not much point arguing about this - it simply isn't direct evidence, pro or con.
>your mind is made up and you believe in viral persistence
..
>only referencing studies that support your point of view
not so - as noted above, in addition to Maylin'08 there are two other recent studies that report no finding of post-SVR HCV RNA in PBMCs (and all three failed to apply mitogen stimulation of cells prior to PCR). The list of research TN has compiled on the 'occult' health page speaks for itself. If you believe it's one-sided you should extend it; I'll be surprised if TN has missed much.
And BTW, his most recent addition (Hoare'08, he now seems to be adding pre-prints even before publication! you'd think keeping that hair-do in shape wouldn't leave him much time) concludes with
"Non-viremic HCV-antibody positive patients have a liver biopsy that is usually abnormal. Fibrosis was present in most with similar inflammatory infiltrate to viremic cases. The presence of a CD8+T rich inflammatory infiltrate suggests an ongoing immune response in the liver, supporting the view that HCV may persist in the liver in the majority of HCV-RNA negative cases"
None of these patients had undergone tx, their HCV-RNA und status is due to their unaided immune respose. However, as I recall, you were arguing a while back that all SVRs are created equal..
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