Aa
Effect of Peginterferon Alfa-2a (Pegasys) on Liver Histology in Chronic HCV
This is very good news and adds evidence to the histolgic effects of interferon.
If anyone doesn't achieve the "12 week 2 log drop" magic number this is a good study to show to the doctors if they want you to stop treatment.
If anyone doesn't achieve the "12 week 2 log drop" magic number this is a good study to show to the doctors if they want you to stop treatment.
"no significant reduction was observed among nonresponders"
This is not great news for those who do not respond.
Unfortunately for those who do not, the rates of histological progression is back to where it was within one to two years and can be worse in some patients.
So, for those with mild histology to begin with, who are female or who have low risk for progression, and who are genotype 1, this might be something to consider before making the decision to treat. Women of childbearing age also have issues to consider with regard to Interferon therapy.
Here is an <a href="http://www.http://www.hcop.org/hcvinfo/articles/index.cfm?articleid=65">article on that.</a>
I hope this helps,
thanbey
This is not great news for those who do not respond.
Unfortunately for those who do not, the rates of histological progression is back to where it was within one to two years and can be worse in some patients.
So, for those with mild histology to begin with, who are female or who have low risk for progression, and who are genotype 1, this might be something to consider before making the decision to treat. Women of childbearing age also have issues to consider with regard to Interferon therapy.
Here is an <a href="http://www.http://www.hcop.org/hcvinfo/articles/index.cfm?articleid=65">article on that.</a>
I hope this helps,
thanbey
<a href="http://www.hcop.org/hcvinfo/articles/index.cfm?articleid=65">article on that</a>
Rats! I thought I was getting this down...........
sorry about that
thanbey
Rats! I thought I was getting this down...........
sorry about that
thanbey
Can you please tell me the meds that cause liver failure? I am almost 4 months post tx and I still feel like ****! I am geno 1a, and I hope I haven't replased. Thank-you so much! Much love and many prayers, Cindee
I am a non-responder who was in treatment 18 months ago.
After reading the articles I am now seriously considering to stop treatment.. I now feel that I have false hope and have been in denial.. Thank you for the reality check. EDGAR
After reading the articles I am now seriously considering to stop treatment.. I now feel that I have false hope and have been in denial.. Thank you for the reality check. EDGAR
Thanks for posting the link to the study and your site.
While it is clear that people who achieve a SVR benefit the most from the antifibrotic effects of peginterferons don't a certain percentage of nonresponders also benefit?
It seems to me that the jury is still out on that question.
We won't know that until the HALT-C (studying Pegasys) and COPILOT (studying PEG-Intron) studies are completed, or later. These, to my knowlegde, are large studies -- both involving over 1000 patients.
"Both studies will attempt to determine whether long-term treatment with low-dose pegylated interferon can help delay the development of fibrosis and cirrhosis, slow the progression from compensated to decompensated cirrhosis, and reduce the chances of developing liver cancer (hepatocellular carcinoma)."
How long after completing treatment does it take for any benefit to show up in a biopsy? Two years? Five? One?
Best,
Scott
While it is clear that people who achieve a SVR benefit the most from the antifibrotic effects of peginterferons don't a certain percentage of nonresponders also benefit?
It seems to me that the jury is still out on that question.
We won't know that until the HALT-C (studying Pegasys) and COPILOT (studying PEG-Intron) studies are completed, or later. These, to my knowlegde, are large studies -- both involving over 1000 patients.
"Both studies will attempt to determine whether long-term treatment with low-dose pegylated interferon can help delay the development of fibrosis and cirrhosis, slow the progression from compensated to decompensated cirrhosis, and reduce the chances of developing liver cancer (hepatocellular carcinoma)."
How long after completing treatment does it take for any benefit to show up in a biopsy? Two years? Five? One?
Best,
Scott
When I was diagnosed, it was after complete liver failure. After 16 mos. I finally found a G.I. to tx. me. I have now been on pegasys/copegus for 14/24. I'm a 2b. I nearly had liver failure again, but because of other drugs prescribed, and now 4 weeks later feel better. My enzymes are in the normal range for the 1st time since I was diagnosed. My liver has gotten almost back to normal size from inflamation going away. It's not been easy and I'm not done yet, but so far, I thank God everyday for this chance. They will(Hopefully) take my first PCR since beginning tx. Monday. I started at 5 million. I live in nowhere , Mont. so I don't know how they'll get the testing done, but if there's a way, she'll get it done. Hope this helps, inspires someone. They only approved tx. for my condition in July, 2003, so this is all in God's hands. Joni
A certain amount of those who respond to treatment DO have some histological benefit, but only as long as they remain on the interferon. Once interferon is discontinued, histology worsens over the next 1-2 years and even MAY increase.
So, yes, it is possible that non-responders can be maintained and receive a certain amount of histological improvement as long as they are on low dose monotherapy.
When you break it down, it looks like this:
Less than 50% of genotype 1's realize an SVR and of that some, but not all, have some histological benefit.
Those who do not respond, may have to be on interferon for a long time or intermittently for a long time, perhaps life (like insulin for diabetics) if they can tolerate the medications.
That is why, since most people do not progress or die of hepatitis C once they are diagnosed, it is really important to assess whether the risks (sides, adverse events, and possible non-responde) outweight the benefits. There has been at least one study out of the Harvard School of Public Health that concluded that the risks do outweigh the benefits for those (particulalry women) who have mild disease.
So, it isn't a matter of whether treatment is good, bad or ugly. It is a matter of optimal timing and the real likelihood that there are better options coming along for those who can wait. It might just be that those who can, should. This is one of the reasons Roche has been very careful about the 12 week PCR result. There AMY be less risk of being interferon dependent if those who probably are not going to respond discontinue if the 12 week PCR is still positive or has not revealed a 2 log drop in viral load.
I hope this helps.
thanbey
<a href="http://www.hcop.org">Hepatitis C Outreach Project</a>
So, yes, it is possible that non-responders can be maintained and receive a certain amount of histological improvement as long as they are on low dose monotherapy.
When you break it down, it looks like this:
Less than 50% of genotype 1's realize an SVR and of that some, but not all, have some histological benefit.
Those who do not respond, may have to be on interferon for a long time or intermittently for a long time, perhaps life (like insulin for diabetics) if they can tolerate the medications.
That is why, since most people do not progress or die of hepatitis C once they are diagnosed, it is really important to assess whether the risks (sides, adverse events, and possible non-responde) outweight the benefits. There has been at least one study out of the Harvard School of Public Health that concluded that the risks do outweigh the benefits for those (particulalry women) who have mild disease.
So, it isn't a matter of whether treatment is good, bad or ugly. It is a matter of optimal timing and the real likelihood that there are better options coming along for those who can wait. It might just be that those who can, should. This is one of the reasons Roche has been very careful about the 12 week PCR result. There AMY be less risk of being interferon dependent if those who probably are not going to respond discontinue if the 12 week PCR is still positive or has not revealed a 2 log drop in viral load.
I hope this helps.
thanbey
<a href="http://www.hcop.org">Hepatitis C Outreach Project</a>
I was in a study for people like you and obviously me. I started May 2002, fin'ed Oct 2002. Stupid or lucky me, I didn't realize that anyone would hesitate to tx after liver failure. And what a shame. After all, I cl'ed in only 18d's, fin 24wks-2b.
If I hadn't tx'ed, I'ld be dead.
You asked how I was. Well, I'm good b/have to watch for fluid build up. I'm looking for a good mild herbal diuritic. Also, the encephalitis-ammonia thing. Its just a balance of diet, exercise and rest. I feel much better, so good in fact, that I have to pace myself, b/c my energy is not boundless anymore.
I feel as if my liver has really improved since the hep c is gone. And I've learned not to add further insult to the liver's injuries. The longer I stay away from drugs and alcohol, the more I realize I no longer need or want them. And my liver thanks me, too. It's kinda like a pet now.
If I hadn't tx'ed, I'ld be dead.
You asked how I was. Well, I'm good b/have to watch for fluid build up. I'm looking for a good mild herbal diuritic. Also, the encephalitis-ammonia thing. Its just a balance of diet, exercise and rest. I feel much better, so good in fact, that I have to pace myself, b/c my energy is not boundless anymore.
I feel as if my liver has really improved since the hep c is gone. And I've learned not to add further insult to the liver's injuries. The longer I stay away from drugs and alcohol, the more I realize I no longer need or want them. And my liver thanks me, too. It's kinda like a pet now.
Edgar...what is your latest 12 week testing show? I know you said you didn't respond 1st round but how are you doing this time? I can only understand how you are feeling as all this reading of studies etc...can get you down big time. If you are SVR..Great...you know you did good but on the otherhand if you are a 1...and have relapse..then you are thinking..am I progressing things along on my liver? I'm like you as I get going and excited about beating this and then read more, do more reseach and then wonder if I'm doing the right thing. Its like a catch 22! My prayers are with you and I pray you don't give up at this stage of the game.
Thank you both for reaching out. I am starting to feel that ignorance is truly bliss..
I feel that at many times this forum has been very helpful, and many times it has been a depressant.
Maybe the time has come for me to put this forum down for a while.
Thank you ... Edgar
I feel that at many times this forum has been very helpful, and many times it has been a depressant.
Maybe the time has come for me to put this forum down for a while.
Thank you ... Edgar
Sometimes taking a break can help and I know at times reading different postings can make or break the day. I know at times when having a bad day...you quickly forget about it the next and things are so much brighter. Don't make any drastic decisions today but wait..and the answers will come. If you just want to talk...my email ***@****
You're saying that people who achieve a SVR only have a histological benefit if they remain on treatment? No, that simply isn't true.
I don't believe that enough studies have been done to give a final answer on peginterferons as antifibrotics. That is the reason for the HALT-C and COPILOT studies.
Sure, someone with mild damage has time to wait -- perhaps. That would depend on disease progression etc. and that's something that can't be 'predicted' in a linear matter. 'Usually' disease progression is slow but in some cases it isn't.
<a href="http://www.hepcassoc.org/news/article4.html">Antifibrotic Effect of Interferon Alfa in the Treatment of Chronic Hepatitis C:
An Unanticipated but Important End Point
</a>
I don't believe that enough studies have been done to give a final answer on peginterferons as antifibrotics. That is the reason for the HALT-C and COPILOT studies.
Sure, someone with mild damage has time to wait -- perhaps. That would depend on disease progression etc. and that's something that can't be 'predicted' in a linear matter. 'Usually' disease progression is slow but in some cases it isn't.
<a href="http://www.hepcassoc.org/news/article4.html">Antifibrotic Effect of Interferon Alfa in the Treatment of Chronic Hepatitis C:
An Unanticipated but Important End Point
</a>
I also want to say that I am not trying to get into a 'debate' with you over this stuff. It can only help if we talk about it honestly. If I am off base, simply wrong, or obviously nuts tell me. I am just a patient ... diagnosed a little more than one year ago.
Take care,
Scott
Take care,
Scott
I am sorry that that is where the data from HALTC and other studies have taken us so far. APRICOT is a study for those co-infected with HIV and this is a completely different set of circumstances that moninfected people face. I wouldn't take the conclusions for those with HIV and apply them to someone with HCV only. And we haven't even begun to get into gender specific issues, and extrahepatic HCV disease (for which there is mounting evidence, some conclusive)
This is information given by Jay Hoofnagel to the FDA during the approval hearing for Pegasys.
There is a link to the FDA transcript at the bottom of the article previously posted.
I am sorry, it is true. At least, from what is known so far.
That is what interferon and/or ribivirin maintenance therapy is all about. (see link below)
Yeah...... I know, it shocked me, too. But there it is in the hearing transcript. This is the best of the best on the part of the manufacturer in order to have their product FDA approved. Testimony given by HALTC researchers. Not statements to take lightly.
Still, for those who have enough liver damage and no contraindications for interferon therapy, the risk is still worth considering. For those who can wait, that is an option worth thinking seriously about.
Please don't shoot the messenger!
I hope this helps,
thanbey
<a href="http://www.hcop.org/hcvinfo/articles/index.cfm?articleid=62">article ribivirin mintenance therapy</a>
This is information given by Jay Hoofnagel to the FDA during the approval hearing for Pegasys.
There is a link to the FDA transcript at the bottom of the article previously posted.
I am sorry, it is true. At least, from what is known so far.
That is what interferon and/or ribivirin maintenance therapy is all about. (see link below)
Yeah...... I know, it shocked me, too. But there it is in the hearing transcript. This is the best of the best on the part of the manufacturer in order to have their product FDA approved. Testimony given by HALTC researchers. Not statements to take lightly.
Still, for those who have enough liver damage and no contraindications for interferon therapy, the risk is still worth considering. For those who can wait, that is an option worth thinking seriously about.
Please don't shoot the messenger!
I hope this helps,
thanbey
<a href="http://www.hcop.org/hcvinfo/articles/index.cfm?articleid=62">article ribivirin mintenance therapy</a>
To be clear: first I spelled ribavirin wrong, sorry.
Second, the studies shared by the above posters DO show histological response at six months post treatment. I take no issue with those results.
The missing link is what the HALT-C is showing and that is reflected in Dr. Hoofnagel's comments at the FDA: the histological benefit runs out at 1-2 years post treatment and may begin to worsen the fibrosis. Unless those studies went out beyond 2 years, they are not going to show similar results because at the end of treatment (six months post treatment) an person with an SVR can expect to have a histological improvement, but not beyond 2 years after treatment.
So, all of the statements above are true, but it is important to know the parameters of the study in order to understand what conclusions can be drawn from the data and to know the limitations of the data.
I don't see a lot talk about this. But, going to the FDA hearing transcripts, where there is no marketing or conflicts of interest to be had will give the community a glimpse in to the information that we are not getting otherwise.
I couldn't agree more that discussion are useful. It is so hard to sort through the marketing and the science and try to distinquish one from another. I am not concerned about being right, I am concerned that patients and doctors are not being fully informed so that decisions can be made on all the information available. The decisions themselves are completely between a patients and their provider.
I hope this ehlps,
thanbey
Second, the studies shared by the above posters DO show histological response at six months post treatment. I take no issue with those results.
The missing link is what the HALT-C is showing and that is reflected in Dr. Hoofnagel's comments at the FDA: the histological benefit runs out at 1-2 years post treatment and may begin to worsen the fibrosis. Unless those studies went out beyond 2 years, they are not going to show similar results because at the end of treatment (six months post treatment) an person with an SVR can expect to have a histological improvement, but not beyond 2 years after treatment.
So, all of the statements above are true, but it is important to know the parameters of the study in order to understand what conclusions can be drawn from the data and to know the limitations of the data.
I don't see a lot talk about this. But, going to the FDA hearing transcripts, where there is no marketing or conflicts of interest to be had will give the community a glimpse in to the information that we are not getting otherwise.
I couldn't agree more that discussion are useful. It is so hard to sort through the marketing and the science and try to distinquish one from another. I am not concerned about being right, I am concerned that patients and doctors are not being fully informed so that decisions can be made on all the information available. The decisions themselves are completely between a patients and their provider.
I hope this ehlps,
thanbey
Well, gee ...
You're saying that a patient's liver who is 'cured' (and let's define 'cure' to equal a sustained virologic response) becomes worse two years out? Or do you mean in non-responders? THAT I could see but in responders? I know of people that attain a SVR that go on to develop HCC ... yes, but how many? Not too many, more than likely. If the virus is not attacking the liver why would the fibrosis progress? Do we have some data showing that to be the case 2-4 years out? Dr. Hoofnagel says that this "may" happen? I am not clear on it.
You're saying that a patient's liver who is 'cured' (and let's define 'cure' to equal a sustained virologic response) becomes worse two years out? Or do you mean in non-responders? THAT I could see but in responders? I know of people that attain a SVR that go on to develop HCC ... yes, but how many? Not too many, more than likely. If the virus is not attacking the liver why would the fibrosis progress? Do we have some data showing that to be the case 2-4 years out? Dr. Hoofnagel says that this "may" happen? I am not clear on it.
You really are a Honey. You could not have picked a better name. I promise not to make any drastic decisions. Thank you again for reaching out. May Gods graces continue to be with you. Sincerely, Edgar
To my knowledge these studies are ongoing ...
MAINTENANCE THERAPY STUDIES
Recent research has suggested that maintenance therapy of interferon may delay histology or hepatitis disease progression. Histological improvement is observed in some nonresponders to interferon or interferon/ribavirin therapy. This observation has given impetus to begin two large studies to test the concept of low dose interferon maintenance therapy.
Dr.Mitchell Shiffman conducted a small randomized, controlled trial to determine if maintenance interferon therapy could prevent histological progression in a subset of nonresponders (Gastroenterology 1999;117:1164-1172). Fifty-three patients with chronic HCV were enrolled. All were HCV-RNA positive after 6 months of treatment with interferon alfa-2b but had a histological response. Twenty-seven of the patients were randomly assigned to continue interferon (3 MU 3 times weekly) for 24 months; 26 patients discontinued treatment and were observed prospectively. Alanine aminotransferase (ALT) level and HCV-RNA titer were monitored, and liver biopsy was repeated every 12 months. Abstract reported--Before interferon therapy, the 2 groups were well matched for all demographic factors, serum ALT (94.0
MAINTENANCE THERAPY STUDIES
Recent research has suggested that maintenance therapy of interferon may delay histology or hepatitis disease progression. Histological improvement is observed in some nonresponders to interferon or interferon/ribavirin therapy. This observation has given impetus to begin two large studies to test the concept of low dose interferon maintenance therapy.
Dr.Mitchell Shiffman conducted a small randomized, controlled trial to determine if maintenance interferon therapy could prevent histological progression in a subset of nonresponders (Gastroenterology 1999;117:1164-1172). Fifty-three patients with chronic HCV were enrolled. All were HCV-RNA positive after 6 months of treatment with interferon alfa-2b but had a histological response. Twenty-seven of the patients were randomly assigned to continue interferon (3 MU 3 times weekly) for 24 months; 26 patients discontinued treatment and were observed prospectively. Alanine aminotransferase (ALT) level and HCV-RNA titer were monitored, and liver biopsy was repeated every 12 months. Abstract reported--Before interferon therapy, the 2 groups were well matched for all demographic factors, serum ALT (94.0
With all due respect to Doug Dietrick, he is not a neurologist. The researchers doing this work are: Forton in the UK, Aronow (a neurovirologist) in the USA, Firenza in Switzerland.
Since I am not a doctor and certainly not a researcher in neurovirology, I can only tell you that Dr. Aronow has personally told me that the size of the pegylated molecule is too large to cross the blood brain barrier.
You can ask Dr. dietrick the question, but sadnly, I cannot agree that his expertise extends into this area. It could, though. Maybe he knows something the other researchers don't know.
thanbey
Since I am not a doctor and certainly not a researcher in neurovirology, I can only tell you that Dr. Aronow has personally told me that the size of the pegylated molecule is too large to cross the blood brain barrier.
You can ask Dr. dietrick the question, but sadnly, I cannot agree that his expertise extends into this area. It could, though. Maybe he knows something the other researchers don't know.
thanbey
my email is ***@****
been trying to send email unsuccessfully... Edgar
Again thank you for your research on non-responders.
been trying to send email unsuccessfully... Edgar
Again thank you for your research on non-responders.
Douglas T. Dieterich, MD, Contributing Editor
Dr. Dieterich is Vice Chair and Chief Medical Officer Department of Medicine at The Mount Sinai Medical Center. He is also an attending physician at New York University Tisch Hospital, a clinical assistant attending at Bellevue Hospital Center, and an attending physician at Beth Israel North.
A graduate of Yale University, Dr. Dieterich received his medical degree from New York University School of Medicine, and completed his internship and residency in the Department of Internal Medicine, Bellvue Hospital Center.
A fellow of the American College of Physicians and the American College of Gastroenterology, Dr. Dieterich is a member of several professional societies. He has also served on several committees of the AIDS Clinical Trials Group (ACTG) and the National Institutes of Health (NIH), including as a member of the steering committee of the Opportunistic Infections Core Committee, and a member of the Cytomegalovirus (CMV) Committee. He has also served on the NIH Study Sections for CMV and cryptosporidiosis.
Dr. Dieterich has authored numerous journal articles, abstracts, and book chapters on viral hepatitis and AIDS-associated infections of the gastrointestinal tract and liver, and their treatment. He is an internationally-recognized expert on hepatitis C infection and is involved in several research programs evaluating the management treatment of chronic hepatitis C virus (HCV) infection and co-infection with HIV/HCV.
---------------------------
Dieterich doesn't know what he is talking about? Hmmm ...
As I stated before: If you have some proof contradicting the doctor's statement re: the blood brain barrier let us see it. If not I believe the matter is settled.
Dr. Dieterich is Vice Chair and Chief Medical Officer Department of Medicine at The Mount Sinai Medical Center. He is also an attending physician at New York University Tisch Hospital, a clinical assistant attending at Bellevue Hospital Center, and an attending physician at Beth Israel North.
A graduate of Yale University, Dr. Dieterich received his medical degree from New York University School of Medicine, and completed his internship and residency in the Department of Internal Medicine, Bellvue Hospital Center.
A fellow of the American College of Physicians and the American College of Gastroenterology, Dr. Dieterich is a member of several professional societies. He has also served on several committees of the AIDS Clinical Trials Group (ACTG) and the National Institutes of Health (NIH), including as a member of the steering committee of the Opportunistic Infections Core Committee, and a member of the Cytomegalovirus (CMV) Committee. He has also served on the NIH Study Sections for CMV and cryptosporidiosis.
Dr. Dieterich has authored numerous journal articles, abstracts, and book chapters on viral hepatitis and AIDS-associated infections of the gastrointestinal tract and liver, and their treatment. He is an internationally-recognized expert on hepatitis C infection and is involved in several research programs evaluating the management treatment of chronic hepatitis C virus (HCV) infection and co-infection with HIV/HCV.
---------------------------
Dieterich doesn't know what he is talking about? Hmmm ...
As I stated before: If you have some proof contradicting the doctor's statement re: the blood brain barrier let us see it. If not I believe the matter is settled.
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