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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.
I have the whole study if anyone wants it just email me....
jim/apache: regardless of the scary headline, I don't believe possible transmission by svrs was the point of the article (
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That was mostly our point. Indeed, it certainly wasn't what was proved and therefore I question how responsible they were in some of the inferences.
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That was mostly our point. Indeed, it certainly wasn't what was proved and therefore I question how responsible they were in some of the inferences.
co/mike/trish: I've never heard of past ifn tx as grounds for rejecting a potential organ donor, though it's not an area I've read anything about (any references?) As Trish points out, auto-immune disorders, possibly ifn-triggered, could be readily diagnosed so excluding donors (living or dead) on the grounds of ifn exposure seems limiting
The MacParland paper's refs 13-17 address the organ infectivity topic. Though I didn't see any answer to my question above about transmission from SVR-donated organs one of the refs
http://www.ncbi.nlm.nih.gov/pubmed/12942451
may be relevant. They considered *aggressive* (5MU daily!!) pre-transplant tx of 20 pts to clear hcv to avoid re-infection. Among the 12 SVRs, only four "did not have evidence of HCV recurrence after OLT" implying that in most cases SVR status was not sufficient to prevent re-infection.
mb: as jim points out, the paper at the hepatology journal site should be free-access. My understanding of the use of the Ab and IFN tests in inhibiting infection was simply to demonstrate that their assays do in fact reflect infection rather than spurious results. If the PCR and viral protein detection assays were picking up junk, they would continue to do regardless of whether you incubated with Abs/ifn; infection on the other hand would be expected to be blocked, as it is.
jim/apache: regardless of the scary headline, I don't believe possible transmission by svrs was the point of the article (good reason to read the paper rather the summary). The main results seem to be (1) residual virus has demonstrated ability to infect (an open question up to now) and (2) the ability of commercial/clinical VL tests to detect complete absence of virus is suspect (and there is now a separate test for determining presence of virus that does not rely entirely on RNA amplification).
The fact that they had to stimulate PBMCs as part of the detection and infection protocols doesn't seem unusual. We know immune cells are not the virus' preferred hunting ground so having to stimulate those cells to raise viral activity to detectable levels seems reasonable.
The MacParland paper's refs 13-17 address the organ infectivity topic. Though I didn't see any answer to my question above about transmission from SVR-donated organs one of the refs
http://www.ncbi.nlm.nih.gov/pubmed/12942451
may be relevant. They considered *aggressive* (5MU daily!!) pre-transplant tx of 20 pts to clear hcv to avoid re-infection. Among the 12 SVRs, only four "did not have evidence of HCV recurrence after OLT" implying that in most cases SVR status was not sufficient to prevent re-infection.
mb: as jim points out, the paper at the hepatology journal site should be free-access. My understanding of the use of the Ab and IFN tests in inhibiting infection was simply to demonstrate that their assays do in fact reflect infection rather than spurious results. If the PCR and viral protein detection assays were picking up junk, they would continue to do regardless of whether you incubated with Abs/ifn; infection on the other hand would be expected to be blocked, as it is.
jim/apache: regardless of the scary headline, I don't believe possible transmission by svrs was the point of the article (good reason to read the paper rather the summary). The main results seem to be (1) residual virus has demonstrated ability to infect (an open question up to now) and (2) the ability of commercial/clinical VL tests to detect complete absence of virus is suspect (and there is now a separate test for determining presence of virus that does not rely entirely on RNA amplification).
The fact that they had to stimulate PBMCs as part of the detection and infection protocols doesn't seem unusual. We know immune cells are not the virus' preferred hunting ground so having to stimulate those cells to raise viral activity to detectable levels seems reasonable.
I would say the odds of an SVR`er passing it on to another has to be very low...the new sensitve tests they use to detect the virus in an SVR patient can only be done in liver samples...until the new sensitive tests can be done on blood serum...we wont know for 100%...just my thinking
***So where does that leave the real-real world transmission risk for an SVR***
where viral load is either zero or under the radar of the most sensitive commercial tests, depending on who you read?
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Well, as long as you asked Jim...
Imo, it leaves a UNDETECTABLE real world transmission chance.
apache
where viral load is either zero or under the radar of the most sensitive commercial tests, depending on who you read?
============================================================
Well, as long as you asked Jim...
Imo, it leaves a UNDETECTABLE real world transmission chance.
apache
I've seen all of that and I still would bet that you're wrong. And I have seen other recent studies which don't support the position that HCV+ livers have better outcomes than HCV- livers. As you said, it's your opinion, and I don't think you're right. But, we're both probably safe because there isn't any documented examples to site. I'm sensitive about transplantation and SVR so I am less apt to speculate in this area or see speculation without responding.
Mike
Mike
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