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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.”
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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
I won't be shocked if we shortly have a study posted on the prevleance of diabetes and/or IR in the Afro American population LOL and honestly do not know if that was screened out or not. But the other point, is once again the importance of very early viral kinetics in the treatment process.
Here's the full text version and apparently IR was not implicated but haven't had a chance to thorougly digest.
http://www.journals.uchicago.edu/doi/pdf/10.1086/597385
http://www.journals.uchicago.edu/doi/pdf/10.1086/597385
Actually Jim, Latinos have a higher response rate to treatment than African Americans but also have a significantly higher rate of IR/Diabetes. Studies are just starting to appear regarding some of these differences.
I need to clarify....just looked at my notes. It is latinos from Puerto Rico that have the highest rate of type 2 diabetes, about 14% diagnosed. African Americans have approximately 11.5% when both genders are looked at.
www.nih.gov/about/researchresultsforthepublic/Type2Diabetes.pdf
how dare you keep relevant info from your members!
bandman
how dare you keep relevant info from your members!
bandman
??? I'm confused. Are you saying you posted a study in this thread and had it deleted? Well, my ex-girlfriend told me I had certain powers, but one of them is not the ability to delete posts on a forum I do not run. Nor did I contact MH to remove any post regarding diabetes? Why would I. If you had a post deleted, the appropriate thing would be to contact MH and ask why instead of throwing allegations around.
I said previously: "....if that was screened out..."
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Maybe the phrase above is what disturbs you? I was not talking about a post being "screened out", I was talking about IR/diabetes screened out of the study. In other words did the study screen out IR/diabetes as an active factor in the study. You will note that in my next post I mention that apparently that is not the case and posted the full-text. I think you had best read a little more carefully or ask for clarification before jumping down someone's throat.
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Maybe the phrase above is what disturbs you? I was not talking about a post being "screened out", I was talking about IR/diabetes screened out of the study. In other words did the study screen out IR/diabetes as an active factor in the study. You will note that in my next post I mention that apparently that is not the case and posted the full-text. I think you had best read a little more carefully or ask for clarification before jumping down someone's throat.
yes, it was deleted.
all i did was post
www.nih.gov/about/researchresultsforthepublic/Type2Diabetes.pdf
saying that this was common knowlege.
I jumped to conclusions and assumed that you had my post deleted. I apologize.
I don't have to report this to MH because apparently he already knows.... someone is taking down posts as soon as they go up. you may not even have time to read this! lol.
they already took down Cocksparrows thread.
I thought I would give this site another chance , but apparently freedom of speech is not tolerated here
sad.
bandman has left the building.
all i did was post
www.nih.gov/about/researchresultsforthepublic/Type2Diabetes.pdf
saying that this was common knowlege.
I jumped to conclusions and assumed that you had my post deleted. I apologize.
I don't have to report this to MH because apparently he already knows.... someone is taking down posts as soon as they go up. you may not even have time to read this! lol.
they already took down Cocksparrows thread.
I thought I would give this site another chance , but apparently freedom of speech is not tolerated here
sad.
bandman has left the building.
And btw the person I was referring to who in terms of "we shortly have a study posted" was not you, it was CO (she has posted before on IR and Afro Americans) and it was a lighthearted joke with no offense intended to her and absolutely no reference to you.
Apology accepted and frankly I have no idea why that post would have been deleted. We post links all the times here to studies. In fact, I just did earlier. LOL. Do us all a favor and nicely ask MH why they deleted your post and let us know. No harm. No foul. Let the band play on :)
thanks for this one!! It sounds on the surface very bad for africans, but there is good news.
Now they'll have something more specific to focus on, this peculiar response...and research into it may prove of benefit to us all.
I hope Jim you'll keep us posted on what studies follow up this finding....it could be an important key in unlocking a better immune response.
mb
Now they'll have something more specific to focus on, this peculiar response...and research into it may prove of benefit to us all.
I hope Jim you'll keep us posted on what studies follow up this finding....it could be an important key in unlocking a better immune response.
mb
Is it possible to discuss the other matter in a new thread and keep this one on topic. It's a good topic and I really don't feel like reposting everything because this thread no doubt will be deleted the way it's going.
That is very strange.... I did not even see your name on that thread... they must have mistakenly addressed you instead of the ppl arguing on that thread
Be careful posting MH’s responses. I once did and was threatened suspension or being banned.
Sorry Jim, you're right. We better get back to topic.
Thanks for posting this... I am quite sure that I did not RVR because of my partial African American descent. I hope that extending treatment will have done it's job. We'll see in ca 5 weeks.
Thanks for posting this... I am quite sure that I did not RVR because of my partial African American descent. I hope that extending treatment will have done it's job. We'll see in ca 5 weeks.
Your study is very interesting Jim. Thanks for providing us with this information and I hope the conversation stays on task. That would be nice for a change.
Between 4 and 8.... VL under 80 at 4 weeks....
Ended up extending according to formula 8 + 24 = 32
Ended up extending according to formula 8 + 24 = 32
interesting does that mean we should get a viral load test after the first week of tx to see how we respond sorry I did not read the link but that would seem resonable to have a test done on the onset of the treatment for possibilities or am I not understanding
baja
baja
PegIFN had to be synthesized from somebody's natural IFN originally, Ja? Probably Caucasian.
I'm not as up on geno 2 and 3 protocols as with geno 1. That said, your plan sounds like a good one and I will be waiting for your SVR post. How many weeks post tx are you now?
-- Jim
-- Jim
Thanks Jim. I'm geno 3a... I got 9 days of meds to go...
Actually you are one of the people who has given me loads of knowledge and good advice since I joined the forum... I will always be grateful for that!
Actually you are one of the people who has given me loads of knowledge and good advice since I joined the forum... I will always be grateful for that!
Most studies still revolve around the week 4 test in terms of predictive power. That said, smaller studies have been coming out of years where testing has been done as early as 24 hours after the first injection and indeed I believe some of the PI trials test that early but not sure. This study deals with DAY 2, not "week 2" . FWIW when I treated three years ago I tested for viral load weekly from week 1 until I was UND at week 6. Very few here test that often but my doc suggested it and frankly I was thrilled he was being so thorough. And frankly, if I had to treat again, I'd probably ask for the both the 24 hour test as well as the day 2 test as well, but this does not mean it would have a solid current clinical signifcance nor am I suggesting anyone test viral load other than week 4 or weekly until UND if they really want to follow things closely.
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