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Two-Day Results Predict Ultimate Response to Therapy in Chronic Hepatitis C
Two-Day Results Predict Ultimate Response to Therapy in Chronic Hepatitis C
A new study suggests that previously noted low rates of successful hepatitis C virus (HCV) therapy in African Americans are in large part due to very early differences in the antiviral activity induced by interferon. The study is published in the April 15 issue of The Journal of Infectious Diseases, now available online.
More than 3 million Americans are infected with HCV, and in some countries more than 10 percent of the population is infected. Chronic HCV infection is the leading cause of liver failure worldwide. Response to standard therapy with peginterferon and ribavirin varies widely. Those infected with one strain of the virus—genotype 1—are the least likely to have a successful response to therapy, known as a sustained virological response (SVR). About one-half of patients infected with genotype 1 do not achieve SVR.
Studies have shown that African Americans have consistently lower rates of SVR to interferon-based therapy, compared to Caucasian Americans. A recent study of those with chronic genotype 1 HCV infection found that only 28 percent of African American patients attained SVR, compared with 52 percent in Caucasian Americans. This new study shows that the variation in therapy responsiveness between African Americans and Caucasian Americans can be partly explained by differences in viral response noted as early as one to two days after the first dose of peginterferon.
The study, conducted by a collaborative group of eight medical centers throughout the United States, monitored 341 patients with chronic HCV, genotype 1, who underwent therapy with peginterferon and ribavirin for at least 24 weeks. It focused on response rates to interferon therapy within the first 28 days of therapy, noting viral factors such as HCV RNA levels and host factors such as race, gender, and weight.
Results showed that HCV RNA levels decreased in almost all patients, and that the degree and pattern of decrease, as expected, was different between African and Caucasian Americans. Most important was the new finding that these differences were statistically significant by day 2 of treatment, and that this early viral kinetic measurement was a reliable predictor of ultimate SVR rates. After 28 days of treatment, 22 percent of Caucasian Americans, but only 12 percent of African Americans, were HCV RNA negative.
These findings are particularly important because they point toward the presence of some block or defect in the immediate antiviral response of those who do not respond to therapy. As the authors summarize, “The underlying cause of virological non-response and the reasons why it is more common among African Americans than Caucasian Americans are not clear. [But] the current analyses demonstrated that these differences are fundamentally biologic and become apparent within 24 to 48 hours of starting therapy.” As a next step, future research should focus on these host biologic factors that are induced by interferon in an attempt to improve therapy response rates.
In an accompanying editorial, Andrew W. Tai, MD, PhD, and Raymond T. Chung, MD, of Massachusetts General Hospital agree that the findings will prove vital for future research into HCV, remarking, “[this study] demonstrates that the low rates of SVR in African American patients in response to IFN-based therapy appear to result, in large part, from impaired early viral kinetics. Further studies are necessary to uncover the relevant mechanisms that underlie this defect in IFN signaling… with the hope that such mechanisms can be manipulated to restore interferon responsiveness in the otherwise nonresponsive host.”
###
Founded in 1904, The Journal of Infectious Diseases is the premier publication in the Western Hemisphere for original research on the pathogenesis, diagnosis, and treatment of infectious diseases; on the microbes that cause them; and on disorders of host immune mechanisms. Articles in JID include research results from microbiology, immunology, epidemiology, and related disciplines. JID is published under the auspices of the Infectious Diseases Society of America (IDSA). Based in Arlington, Va., IDSA is a professional society representing more than 8,600 physicians and scientists who specialize in infectious diseases. For more information, visit www.idsociety.org.
http://www.idsociety.org/Content.aspx?id=13720
A new study suggests that previously noted low rates of successful hepatitis C virus (HCV) therapy in African Americans are in large part due to very early differences in the antiviral activity induced by interferon. The study is published in the April 15 issue of The Journal of Infectious Diseases, now available online.
More than 3 million Americans are infected with HCV, and in some countries more than 10 percent of the population is infected. Chronic HCV infection is the leading cause of liver failure worldwide. Response to standard therapy with peginterferon and ribavirin varies widely. Those infected with one strain of the virus—genotype 1—are the least likely to have a successful response to therapy, known as a sustained virological response (SVR). About one-half of patients infected with genotype 1 do not achieve SVR.
Studies have shown that African Americans have consistently lower rates of SVR to interferon-based therapy, compared to Caucasian Americans. A recent study of those with chronic genotype 1 HCV infection found that only 28 percent of African American patients attained SVR, compared with 52 percent in Caucasian Americans. This new study shows that the variation in therapy responsiveness between African Americans and Caucasian Americans can be partly explained by differences in viral response noted as early as one to two days after the first dose of peginterferon.
The study, conducted by a collaborative group of eight medical centers throughout the United States, monitored 341 patients with chronic HCV, genotype 1, who underwent therapy with peginterferon and ribavirin for at least 24 weeks. It focused on response rates to interferon therapy within the first 28 days of therapy, noting viral factors such as HCV RNA levels and host factors such as race, gender, and weight.
Results showed that HCV RNA levels decreased in almost all patients, and that the degree and pattern of decrease, as expected, was different between African and Caucasian Americans. Most important was the new finding that these differences were statistically significant by day 2 of treatment, and that this early viral kinetic measurement was a reliable predictor of ultimate SVR rates. After 28 days of treatment, 22 percent of Caucasian Americans, but only 12 percent of African Americans, were HCV RNA negative.
These findings are particularly important because they point toward the presence of some block or defect in the immediate antiviral response of those who do not respond to therapy. As the authors summarize, “The underlying cause of virological non-response and the reasons why it is more common among African Americans than Caucasian Americans are not clear. [But] the current analyses demonstrated that these differences are fundamentally biologic and become apparent within 24 to 48 hours of starting therapy.” As a next step, future research should focus on these host biologic factors that are induced by interferon in an attempt to improve therapy response rates.
In an accompanying editorial, Andrew W. Tai, MD, PhD, and Raymond T. Chung, MD, of Massachusetts General Hospital agree that the findings will prove vital for future research into HCV, remarking, “[this study] demonstrates that the low rates of SVR in African American patients in response to IFN-based therapy appear to result, in large part, from impaired early viral kinetics. Further studies are necessary to uncover the relevant mechanisms that underlie this defect in IFN signaling… with the hope that such mechanisms can be manipulated to restore interferon responsiveness in the otherwise nonresponsive host.”
###
Founded in 1904, The Journal of Infectious Diseases is the premier publication in the Western Hemisphere for original research on the pathogenesis, diagnosis, and treatment of infectious diseases; on the microbes that cause them; and on disorders of host immune mechanisms. Articles in JID include research results from microbiology, immunology, epidemiology, and related disciplines. JID is published under the auspices of the Infectious Diseases Society of America (IDSA). Based in Arlington, Va., IDSA is a professional society representing more than 8,600 physicians and scientists who specialize in infectious diseases. For more information, visit www.idsociety.org.
http://www.idsociety.org/Content.aspx?id=13720
You're right, we've always been cool, and good to see you posting as well.
Other than the Tuskegee Horror, to help reconcile the "counter-intuitive" nature of minority participation, I do remember a study/survey -- something -- a year or so ago that showed that minorities were more apt to be sent home from the ER as opposed to non-minorities who might have been given a hospital bed and therefore more enhanced care. And for the same diagnosis. So I do wonder if perhaps a prejudice, subconscious or not, exists within the medical community that may give preferential trial assignments to non-minorities.
Another factor no doubt is that because Afro Americans have a significantly lower SVR rate, many trials may have excluded them on that basis because the results would be skewed differently.
-- Jim
Other than the Tuskegee Horror, to help reconcile the "counter-intuitive" nature of minority participation, I do remember a study/survey -- something -- a year or so ago that showed that minorities were more apt to be sent home from the ER as opposed to non-minorities who might have been given a hospital bed and therefore more enhanced care. And for the same diagnosis. So I do wonder if perhaps a prejudice, subconscious or not, exists within the medical community that may give preferential trial assignments to non-minorities.
Another factor no doubt is that because Afro Americans have a significantly lower SVR rate, many trials may have excluded them on that basis because the results would be skewed differently.
-- Jim
There aren't enough derogatory adjectives to sufficiently convey how most Americans today feel about this topic. If they know about it, that is.
ML
ML
Jim,
For the record, I don't believe I have ever responded to a post of yours with cynicism, or even skepticism. Not that I wouldn't if I had reason to. lol ;)
It's been shown that socio-economic factors are directly correlated to HCV infection for all ethnicities. I can't remember all of the stats but those with HCV are in general poorer, less educated, more likely to abuse substances, and come from dysfunctional families significantly greater than the population-at-large.
I'm not sure how these facts would influence minorities more than caucasians when it comes to enrolling in HCV trials. It is somewhat counter-intuitive that those with the least amount of medical care and financial resources wouldn't take advantage of the free medicines and monitoring that a trial offers.
Many African-Americans that I have interacted with over the years concerning HCV have expressed horror at even the simple mention of enrolling in a trial. Some remember Tuskegee----or have been raised by those who do and the spectre of a trial (especially one funded or controlled with the help of the US gov't) has produced a lingering fear that is a quantifiable cultural phenomenon. I have known a researcher with SP for years. She helps to develop trials and has often mentioned over the years how hard it is to get minority participation especially amongst African-Americans, this despite earnest attempts to recruit this population. As a company that sells medicine they would love to have much more data on a segment of the population with high prevalence rates.
It's my belief that the lack of data pertaining to the HCV tx of African-Americans can only be overcome by allaying the fears and sense of mistrust of those who remember Tuskegee or waiting until the clouds of time obscure their collective memory.
I can't believe we did this to US citizens while at the same time we were trying to hunt down Mengele. (Gratuitous cynical remark) ;)
Jim its always nice to see you post and I too hope all is well where you are.
ML
.
For the record, I don't believe I have ever responded to a post of yours with cynicism, or even skepticism. Not that I wouldn't if I had reason to. lol ;)
It's been shown that socio-economic factors are directly correlated to HCV infection for all ethnicities. I can't remember all of the stats but those with HCV are in general poorer, less educated, more likely to abuse substances, and come from dysfunctional families significantly greater than the population-at-large.
I'm not sure how these facts would influence minorities more than caucasians when it comes to enrolling in HCV trials. It is somewhat counter-intuitive that those with the least amount of medical care and financial resources wouldn't take advantage of the free medicines and monitoring that a trial offers.
Many African-Americans that I have interacted with over the years concerning HCV have expressed horror at even the simple mention of enrolling in a trial. Some remember Tuskegee----or have been raised by those who do and the spectre of a trial (especially one funded or controlled with the help of the US gov't) has produced a lingering fear that is a quantifiable cultural phenomenon. I have known a researcher with SP for years. She helps to develop trials and has often mentioned over the years how hard it is to get minority participation especially amongst African-Americans, this despite earnest attempts to recruit this population. As a company that sells medicine they would love to have much more data on a segment of the population with high prevalence rates.
It's my belief that the lack of data pertaining to the HCV tx of African-Americans can only be overcome by allaying the fears and sense of mistrust of those who remember Tuskegee or waiting until the clouds of time obscure their collective memory.
I can't believe we did this to US citizens while at the same time we were trying to hunt down Mengele. (Gratuitous cynical remark) ;)
Jim its always nice to see you post and I too hope all is well where you are.
ML
.
I recall an article from at least a year ago which also stated that a 48 hour test can be highly predictive. I don't have the time to search for it now but I am sure that I read it and I likely have it somewhere.l
Mike
Mike
I did as you said and googled "Tuskegee Experiment". A very interesting but also very disturbing piece of history.
At first, I wrote off you comment to that sharp cynicism that in part makes you "Mr. Liver". But a quick "google" shows some truth although as I suspected minority participation in trials is more complex with socio/economic factors at play. This does however appear to confirm some of the number(s) discrepancy that has been discussed.
http://www.cancer.gov/newscenter/benchmarks-vol6-issue4/page1
Hope this finds you well.
-- Jim
http://www.cancer.gov/newscenter/benchmarks-vol6-issue4/page1
Hope this finds you well.
-- Jim
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