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What Do You Think About This Scary Study?
Study: Patients With Resolved Hepatitis C Likely Still Contagious
Patients with chronic hepatitis C that has been resolved through therapy or immune response may still be able to infect others with the virus. That finding is from a new study in the May issue of Hepatology, a journal published by John Wiley & Sons on behalf of the American Association for the Study of Liver Diseases (AASLD). The article is also available online at Wiley Interscience (www.interscience.wiley.com).
About 170 million people worldwide are infected with hepatitis C virus, which can progress to chronic hepatitis, cirrhosis and even liver cancer. In some individuals, the infection seems to resolve, either spontaneously from the efforts of the immune system, or after treatment with interferon and ribavirin.
Patients who achieve a sustained viral response show no clinical or biochemical evidence of liver disease and standard tests can no longer detect the virus in their blood. However, more sensitive research tests are finding that such patients often still have miniscule amounts of the virus in their bodies. No one knows if these trace remainders are infectious.
Researchers led by Tomasz I. Michalak of Memorial University of Newfoundland, Canada examined this question using a system that allows for propagation of HCV in human T cells in vitro.
They began with nine patients with HCV who had achieved a sustained viral response that persisted for at least two years after treatment. HCV RNA was detectable in their blood only with the more sensitive tests.
The researchers set up twelve cultures of lymphoid cells from healthy donors, and exposed them to plasma or to supernatants of cultured circulating lymphoid cells from the HCV patients. Eleven of the cell cultures became HCV RNA positive. Furthermore, HCV from three of the nine patients was able to establish active HCV replication in the cultures.
“These findings provide in vitro evidence that trace quantities of HCV persisting in the circulation for a long time after therapeutically induced resolution of CHC can remain infectious,” the authors report.
Interestingly, HCV replication in the T cells was prevented after neutralization of the virus, and by treatment with interferon.
This study is the first to investigate the infectivity of HCV traces that remain when the infection is occult. It agrees with previous animal studies of the same question.
“Our present findings reveal that HCV circulating in some individuals with resolved hepatitis C is capable of inducing productive infection in vitro at doses of 20 to 50 copies,” the authors conclude. “This can be interpreted as a strong indication of potential virus infectivity in vivo.”
Article: “Hepatitis C Virus Persisting at Low Levels after Clinically Apparent Sustained Virological Reponse to Antiviral Therapy Retains Its Infectivity in Vitro.” MacParland, Sonya A.; Pham, Tram N.Q.; Guy, Clifford S.; Michalak, Tomasz I. Hepatology; May 2009.
Patients with chronic hepatitis C that has been resolved through therapy or immune response may still be able to infect others with the virus. That finding is from a new study in the May issue of Hepatology, a journal published by John Wiley & Sons on behalf of the American Association for the Study of Liver Diseases (AASLD). The article is also available online at Wiley Interscience (www.interscience.wiley.com).
About 170 million people worldwide are infected with hepatitis C virus, which can progress to chronic hepatitis, cirrhosis and even liver cancer. In some individuals, the infection seems to resolve, either spontaneously from the efforts of the immune system, or after treatment with interferon and ribavirin.
Patients who achieve a sustained viral response show no clinical or biochemical evidence of liver disease and standard tests can no longer detect the virus in their blood. However, more sensitive research tests are finding that such patients often still have miniscule amounts of the virus in their bodies. No one knows if these trace remainders are infectious.
Researchers led by Tomasz I. Michalak of Memorial University of Newfoundland, Canada examined this question using a system that allows for propagation of HCV in human T cells in vitro.
They began with nine patients with HCV who had achieved a sustained viral response that persisted for at least two years after treatment. HCV RNA was detectable in their blood only with the more sensitive tests.
The researchers set up twelve cultures of lymphoid cells from healthy donors, and exposed them to plasma or to supernatants of cultured circulating lymphoid cells from the HCV patients. Eleven of the cell cultures became HCV RNA positive. Furthermore, HCV from three of the nine patients was able to establish active HCV replication in the cultures.
“These findings provide in vitro evidence that trace quantities of HCV persisting in the circulation for a long time after therapeutically induced resolution of CHC can remain infectious,” the authors report.
Interestingly, HCV replication in the T cells was prevented after neutralization of the virus, and by treatment with interferon.
This study is the first to investigate the infectivity of HCV traces that remain when the infection is occult. It agrees with previous animal studies of the same question.
“Our present findings reveal that HCV circulating in some individuals with resolved hepatitis C is capable of inducing productive infection in vitro at doses of 20 to 50 copies,” the authors conclude. “This can be interpreted as a strong indication of potential virus infectivity in vivo.”
Article: “Hepatitis C Virus Persisting at Low Levels after Clinically Apparent Sustained Virological Reponse to Antiviral Therapy Retains Its Infectivity in Vitro.” MacParland, Sonya A.; Pham, Tram N.Q.; Guy, Clifford S.; Michalak, Tomasz I. Hepatology; May 2009.
ML: -just show me one documented case of relapse beyond 3 years SVR which is verifiable and has been peer-reviewed by a reputable scientific body and published. So far no one has been able to do so. This, I'm afraid is the big elephant in Pham's lab.
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Yes, because if the virus is not truly gone like Pham suggests, then it must be the immune system keeping an SVR from relapse. Yet, we don't see relapses in SVRs even in immune compromised individuals. So what's keeping the virus "under the radar"? One explanation is that what they are seeing really isn't the replicative/infectious virus that is known as HCV but some sort of partial/impotent imposter.
------------
Yes, because if the virus is not truly gone like Pham suggests, then it must be the immune system keeping an SVR from relapse. Yet, we don't see relapses in SVRs even in immune compromised individuals. So what's keeping the virus "under the radar"? One explanation is that what they are seeing really isn't the replicative/infectious virus that is known as HCV but some sort of partial/impotent imposter.
I think this topic has sure had legs. I'm willing to bet Pham would happily concur since he's been making a living trying to prove something unsuccessfully for twenty years.
I've wondered for some time why his research seems to avoid employing techniques
that would bolster his findings. Now, I may have missed something and its been awhile but the following are problem points I have with his studies.
He has hung his hat for a long time on the proposition that the neg strand is a sign of replication, ergo, its existence indicates ongoing viral infectivity. To my knowledge its presence is an indication of replication but its discovery is meaningless by itself. This presence of the neg strand does not indicate completion of the replicative process. It is exactly what it is called---an intermediate step (necessary for replication). The pos strand is also an intermediate necessary for the neg strand to do its part in the process. By measuring the presence of both pos and neg strands a ratio of +/- can be estimated and compared to known ratios. I don't believe I've seen this in his studies.
Macrophages (part of the family of white cells known as PBMC) collect viral debris from our blood. By collecting these macrophages and stimulating them to divide at a much faster rate poses some problems for me. Cell division can result in the release of some cell contents each and every time it divides. Along with the crushed cells done by centrifuge one can artificially create a scenario that only exists in vitro and not in nature. The released contents of these cells includes RNA fragments which alone have no ability to infect. However with a large enough sample it can then be amplified by RT-PCR whereby it would detect the presence of the RNA indicating active virus.
I've offered the same challenge for nearly ten years now---just show me one documented case of relapse beyond 3 years SVR which is verifiable and has been peer-reviewed by a reputable scientific body and published. So far no one has been able to do so. This, I'm afraid is the big elephant in Pham's lab.
If I have misinterpeted, misread, or misunderstood, I am prepared to modify my views. I haven'tlooked over any of these studies for some time and I'm working with less than optimum memory lately so its a distinct possibility.
ML
I've wondered for some time why his research seems to avoid employing techniques
that would bolster his findings. Now, I may have missed something and its been awhile but the following are problem points I have with his studies.
He has hung his hat for a long time on the proposition that the neg strand is a sign of replication, ergo, its existence indicates ongoing viral infectivity. To my knowledge its presence is an indication of replication but its discovery is meaningless by itself. This presence of the neg strand does not indicate completion of the replicative process. It is exactly what it is called---an intermediate step (necessary for replication). The pos strand is also an intermediate necessary for the neg strand to do its part in the process. By measuring the presence of both pos and neg strands a ratio of +/- can be estimated and compared to known ratios. I don't believe I've seen this in his studies.
Macrophages (part of the family of white cells known as PBMC) collect viral debris from our blood. By collecting these macrophages and stimulating them to divide at a much faster rate poses some problems for me. Cell division can result in the release of some cell contents each and every time it divides. Along with the crushed cells done by centrifuge one can artificially create a scenario that only exists in vitro and not in nature. The released contents of these cells includes RNA fragments which alone have no ability to infect. However with a large enough sample it can then be amplified by RT-PCR whereby it would detect the presence of the RNA indicating active virus.
I've offered the same challenge for nearly ten years now---just show me one documented case of relapse beyond 3 years SVR which is verifiable and has been peer-reviewed by a reputable scientific body and published. So far no one has been able to do so. This, I'm afraid is the big elephant in Pham's lab.
If I have misinterpeted, misread, or misunderstood, I am prepared to modify my views. I haven'tlooked over any of these studies for some time and I'm working with less than optimum memory lately so its a distinct possibility.
ML
willing,
We hashed this over before,
remember 8 of 9pateints were over 40vl...and you wrote:
=============================================================
" Furthemore, VL in patient 6 (59/F) with a VL of 1600 vge should have been picked up even the Roche Amplicor v2. This discussion and the paper's lack of comment on the discrepancy in VL tests is making me
***see the paper in a new light:***
apart from the main result being reported, the paper is a shot across the bow of all the sensitive VL testing technology. "
=============================================================
Has some new study caused you to 'lose the light' on this willing ?
So once again, researchers take patients that are not SVR (by current available vl tests), and show that they have virus that can replicate when stimulated in a laboratory test tube.
Is this a big surprise, or even a new finding ???
apache
We hashed this over before,
remember 8 of 9pateints were over 40vl...and you wrote:
=============================================================
" Furthemore, VL in patient 6 (59/F) with a VL of 1600 vge should have been picked up even the Roche Amplicor v2. This discussion and the paper's lack of comment on the discrepancy in VL tests is making me
***see the paper in a new light:***
apart from the main result being reported, the paper is a shot across the bow of all the sensitive VL testing technology. "
=============================================================
Has some new study caused you to 'lose the light' on this willing ?
So once again, researchers take patients that are not SVR (by current available vl tests), and show that they have virus that can replicate when stimulated in a laboratory test tube.
Is this a big surprise, or even a new finding ???
apache
Full-text is online here for free:
http://www3.interscience.wiley.com/cgi-bin/fulltext/121581244/HTMLSTART
http://www3.interscience.wiley.com/cgi-bin/fulltext/121581244/HTMLSTART
I've been edited. PM me if you want the whole study. I have it. This place has more rules than a trafffic cop.
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