Aa
Maintenance Interferon -Might have limitedf benefit.
Extended Follow-Up of HALT-C Study Shows Some Benefit of Interferon
Bob Roehr
November 7, 2010 (Boston, Massachusetts) — The utility of maintenance pegylated interferon (PegIFN) therapy to prevent hepatocellular carcinoma (HCC) in patients with advanced chronic hepatitis has been a contentious matter for some time.
The pendulum has swung from support for the idea to early evidence of a lack of efficacy. Now, here at The Liver Meeting 2010: American Association for the Study of Liver Diseases 61st Annual Meeting, longer-term data suggest marginal, limited support for its use. Most surprisingly, data opposing its use — and now for its support — have come from the same study, the ongoing Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) trial.
Anna S. Lok, MD, from the University of Michigan Medical Center in Ann Arbor, presented the latest iteration of data on extended follow-up. "In an earlier report, which included a median follow-up of up to 4.6 years, with a total of 53 HCC cases, we found no difference between the treated and the control groups. The 2 lines basically were identical."
The newer analysis was based on a median of 6.1 years of follow-up. There were "almost double the number of HCC cases, with a total of 88," Dr. Lok reported. The cumulative incidence of HCC at 3, 5, and 7 years for the treated group was 2.3%, 6%, and 8.1%, respectively. Incidence in the control group was 2.5%, 6.2%, and 13.8% at 3, 5, and 7 years, respectively.
"The 2 lines of the Kaplan-Meier Curve completely overlap until the end of year 6, when there is a divergence in the 2 lines, and the P value was not significant," Dr. Lok said.
"However, when we analyzed the data separately, for the fibrosis substratum and the cirrhosis substratum, we saw that the treated group had a significantly lower incidence of HCC compared with the untreated group, with a hazard ratio of 0.45 and a P value of .01."
Subsequent analysis showed that incidence of HCC was significantly lower in patients who had completed at least 2 years of treatment. "They had less advanced liver disease, more normal platelet counts, and normal [aspartate aminotransferase] levels."
Dr. Lok concluded, "Extended follow-up of the HALT-C cohort showed a modest effect of long-term low-dose PegIFN in reducing the incidence of HCC in patients with hepatitis C and cirrhosis, but not in those with advanced fibrosis.
"Given the marginal benefit on HCC, the lack of overall benefit on disease progression, and the side effects of PegIFN, the utility of maintenance PegIFN to prevent HCC in patients with HCV-related cirrhosis who failed to achieve SVR is limited," she acknowledged.
Arun J. Sanyal, MD, American Association for the Study of Liver Diseases president and head of the division of gastroenterology at Virginia Commonwealth University, in Richmond, said, "This, potentially, could be very important."
During the question session, treatment activist Jules Levin said 4 years ago the initial analysis and strong recommendations not to treat "did a lot of damage to patients and to the field. I took issue with the investigators over that" at the time, Mr. Levin said.
Subsequent research and analysis of this trial have shown that they were wrong. "It has done irreparable damage to patients. It is important to take note of this." Mr. Levin said. "Patients and their own clinicians should be able to make their own decision for what benefits them based on a clear understanding of the data."
The National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases is funding the HALT-C trial. The speakers have disclosed no relevant financial relationships.
The Liver Meeting 2010: American Association for the Study of Liver Diseases 61st Annual Meeting: Abstract 214. Presented November 2, 2010.
Bob Roehr
November 7, 2010 (Boston, Massachusetts) — The utility of maintenance pegylated interferon (PegIFN) therapy to prevent hepatocellular carcinoma (HCC) in patients with advanced chronic hepatitis has been a contentious matter for some time.
The pendulum has swung from support for the idea to early evidence of a lack of efficacy. Now, here at The Liver Meeting 2010: American Association for the Study of Liver Diseases 61st Annual Meeting, longer-term data suggest marginal, limited support for its use. Most surprisingly, data opposing its use — and now for its support — have come from the same study, the ongoing Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) trial.
Anna S. Lok, MD, from the University of Michigan Medical Center in Ann Arbor, presented the latest iteration of data on extended follow-up. "In an earlier report, which included a median follow-up of up to 4.6 years, with a total of 53 HCC cases, we found no difference between the treated and the control groups. The 2 lines basically were identical."
The newer analysis was based on a median of 6.1 years of follow-up. There were "almost double the number of HCC cases, with a total of 88," Dr. Lok reported. The cumulative incidence of HCC at 3, 5, and 7 years for the treated group was 2.3%, 6%, and 8.1%, respectively. Incidence in the control group was 2.5%, 6.2%, and 13.8% at 3, 5, and 7 years, respectively.
"The 2 lines of the Kaplan-Meier Curve completely overlap until the end of year 6, when there is a divergence in the 2 lines, and the P value was not significant," Dr. Lok said.
"However, when we analyzed the data separately, for the fibrosis substratum and the cirrhosis substratum, we saw that the treated group had a significantly lower incidence of HCC compared with the untreated group, with a hazard ratio of 0.45 and a P value of .01."
Subsequent analysis showed that incidence of HCC was significantly lower in patients who had completed at least 2 years of treatment. "They had less advanced liver disease, more normal platelet counts, and normal [aspartate aminotransferase] levels."
Dr. Lok concluded, "Extended follow-up of the HALT-C cohort showed a modest effect of long-term low-dose PegIFN in reducing the incidence of HCC in patients with hepatitis C and cirrhosis, but not in those with advanced fibrosis.
"Given the marginal benefit on HCC, the lack of overall benefit on disease progression, and the side effects of PegIFN, the utility of maintenance PegIFN to prevent HCC in patients with HCV-related cirrhosis who failed to achieve SVR is limited," she acknowledged.
Arun J. Sanyal, MD, American Association for the Study of Liver Diseases president and head of the division of gastroenterology at Virginia Commonwealth University, in Richmond, said, "This, potentially, could be very important."
During the question session, treatment activist Jules Levin said 4 years ago the initial analysis and strong recommendations not to treat "did a lot of damage to patients and to the field. I took issue with the investigators over that" at the time, Mr. Levin said.
Subsequent research and analysis of this trial have shown that they were wrong. "It has done irreparable damage to patients. It is important to take note of this." Mr. Levin said. "Patients and their own clinicians should be able to make their own decision for what benefits them based on a clear understanding of the data."
The National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases is funding the HALT-C trial. The speakers have disclosed no relevant financial relationships.
The Liver Meeting 2010: American Association for the Study of Liver Diseases 61st Annual Meeting: Abstract 214. Presented November 2, 2010.
That immediate prior comment seems out of context here. It was intended for a different thread. Maybe DoubleDose has something after all !
The essence of entertainment is the deviation from truth and reality. I've also been leery of Sesame Street for quite a while, who really lives in a garbage can?
That makes sense I suppose. It's kind of like people who don't drive cars get in fewer accident than those that do drive. Thanks.
No fret, if you read Mike's post it's about maintenance pegylated interferon.
They're still using Infergen (consensus interferon) but mostly for those who failed with pegylated interferon. Have you and Willy been hanging out? :)
Trin
They're still using Infergen (consensus interferon) but mostly for those who failed with pegylated interferon. Have you and Willy been hanging out? :)
Trin
Hey isn't the article about infergen? I thought most doctors stopped using that stuff as it wasn't working all that well?
Though the research does reference the benefits as ‘marginal’ and ‘limited’, from my personal standpoint, it’s very gratifying evidence. I have always felt that the HALT-C studies needed a longer range follow-up and wider scope of data. When my husband reached week 72, it was indeed ‘contentious’ as to whether there would be any benefit to him continuing on Interferon, and everyone kept waving the previous HALT-C evidence as reason to discontinue therapy. I had to present considerable data and evidence relative to the anti-oncogenic properties of Interferon to support my husband’s instincts to continue, and this abstract gives us further confidence and definite reinforcement that we were not barking up the wrong tree. Granted, he’s not truly doing ‘maintenance therapy’ because he’s still taking full doses (180mcg) of Peg, but our thinking is it might perhaps further increase his odds of preventing further HCC recurrence, and now that he officially falls into the “treated for 2 years or longer” category, hopefully he will gain whatever benefit ‘maintenance’ might confer, marginal or otherwise. Considering the poor outcomes expected with HCC, he feels it a worthwhile pursuit, especially since thus far he’s done far better than all prognoses.
Thanks for posting this, really made my day. :)
FlGuy:
From a logistical standpoint, I actually think it makes sense that reducing the incidence of HCC in the cirrhotic population would be significant but not nearly so in the fibrotic population. Since HCC is rarely found in hcv patients without pre-existing cirrhosis, the expectation that the incidence of HCC in hcv fibrotics (incidence <1%) would see little reduction (since there isn’t much prevalence to reduce in the first place) actually makes sense to me.
Nygirl7:
That was my understanding of the HALT-C study, too, that it was maintenance therapy for those who had failed SOC. Though not addressed in the article mikesimon posted, I was, however, always curious what benefits (if any) there might be for those cirrhotics who DID reach undetected or SVR, especially because even cirrhotics who SVR are not excluded from possible HCC and ESLD.
HectorSF:
After resection of HCC, my husband was told to expect recurrence within a year (greater than 50% approximate risk) – he started Interferon therapy, and managed to stave off recurrence for over 3 years. Certainly we have no basis for comparison, but my husband remains convinced that SOC has had some benefit (though to what extent, we’ll never know).
~eureka
Thanks for posting this, really made my day. :)
FlGuy:
From a logistical standpoint, I actually think it makes sense that reducing the incidence of HCC in the cirrhotic population would be significant but not nearly so in the fibrotic population. Since HCC is rarely found in hcv patients without pre-existing cirrhosis, the expectation that the incidence of HCC in hcv fibrotics (incidence <1%) would see little reduction (since there isn’t much prevalence to reduce in the first place) actually makes sense to me.
Nygirl7:
That was my understanding of the HALT-C study, too, that it was maintenance therapy for those who had failed SOC. Though not addressed in the article mikesimon posted, I was, however, always curious what benefits (if any) there might be for those cirrhotics who DID reach undetected or SVR, especially because even cirrhotics who SVR are not excluded from possible HCC and ESLD.
HectorSF:
After resection of HCC, my husband was told to expect recurrence within a year (greater than 50% approximate risk) – he started Interferon therapy, and managed to stave off recurrence for over 3 years. Certainly we have no basis for comparison, but my husband remains convinced that SOC has had some benefit (though to what extent, we’ll never know).
~eureka
Background: The HALT-C trial included only patients who failed SOC treatment and had advanced fibrosis and compensated cirrhosis.
Maintenance pegIFN has been reported to decrease the incidence of HCC in pts with CHC (chronic hepatitis). Earlier reports of the HALT-C trial found that maintenance pegIFN did not reduce clinical outcomes during the first 4 yr but the follow-up may have been too short to observe a chemopreventive effect on HCC.
Aim: To determine whether pegIFN decreased the incidence of HCC in the HALT-C cohort with longer follow-up.
Results: After a median follow-up of 6.1 yrs (max 8.7)
PegIFN was associated with a significantly lower incidence of HCC among patients with CIRRHOSIS at baseline but NOT those with advanced fibrosis; cumulative incidence at 8 yrs was 11% vs. 24.2% for patients with cirrhosis. Among patients with cirrhosis at baseline, the cumulative rate of HCC in the two treatment groups did not diverge until after yr 4.
Conclusions: Extended follow-up of the HALT-C cohort showed a modest benefit of long-term pegIFN in decreasing the incidence of HCC. This effect was mainly observed in pts with established cirrhosis and took several yrs to become apparent.
“Given the marginal benefit on HCC, the lack of overall benefit on disease progression, and the side effects of pegIFN, the utility of manintenance pegIFN to prevent HCC in patients with HCV-related cirrhosis who failed to achieve SVR is limited”.
In my words:
So in order for this treatment to be effective, you must have cirrhosis at the start of treatment and be treated with maintenance pegIFN for more then 2 years. The chances of developing HCC will be reduced by about 13%. For persons with advanced fibrosis there is very little benefit. 0.3%.
Hopefully with the addition of more treatment options (STAT C meds) and better screening options in the future most HCV patients will not progress to cirrhosis.
hectorsf
Maintenance pegIFN has been reported to decrease the incidence of HCC in pts with CHC (chronic hepatitis). Earlier reports of the HALT-C trial found that maintenance pegIFN did not reduce clinical outcomes during the first 4 yr but the follow-up may have been too short to observe a chemopreventive effect on HCC.
Aim: To determine whether pegIFN decreased the incidence of HCC in the HALT-C cohort with longer follow-up.
Results: After a median follow-up of 6.1 yrs (max 8.7)
PegIFN was associated with a significantly lower incidence of HCC among patients with CIRRHOSIS at baseline but NOT those with advanced fibrosis; cumulative incidence at 8 yrs was 11% vs. 24.2% for patients with cirrhosis. Among patients with cirrhosis at baseline, the cumulative rate of HCC in the two treatment groups did not diverge until after yr 4.
Conclusions: Extended follow-up of the HALT-C cohort showed a modest benefit of long-term pegIFN in decreasing the incidence of HCC. This effect was mainly observed in pts with established cirrhosis and took several yrs to become apparent.
“Given the marginal benefit on HCC, the lack of overall benefit on disease progression, and the side effects of pegIFN, the utility of manintenance pegIFN to prevent HCC in patients with HCV-related cirrhosis who failed to achieve SVR is limited”.
In my words:
So in order for this treatment to be effective, you must have cirrhosis at the start of treatment and be treated with maintenance pegIFN for more then 2 years. The chances of developing HCC will be reduced by about 13%. For persons with advanced fibrosis there is very little benefit. 0.3%.
Hopefully with the addition of more treatment options (STAT C meds) and better screening options in the future most HCV patients will not progress to cirrhosis.
hectorsf
I always thought maintenance therapy was given to people who did not achieve SVR for some reason - goes to show what I know for reading this forum for the last 5/6 years. I dont know what I thought it was for then I guess I had it all completely backwards there......go figure!
Mike, both patient and doctor started TX with the intention of maintenance, half dose therapy for as long as was needed, possibly several years First viral clearance would be achieved by utilizing full dose SOC for up to 12 weeks, since she had always cleared, but had always relapsed. It was felt that a viral clearance followed by maintenance (in this case it was called suppressive therapy) might be more effective while the half dosing was continued.
In my friends case, when she attained an RVR full dosing WAS continued. My post spoke to the many people who were deterred by the early findings of the HALT-C trials, and decided to wait for any permutation of maintenance or suppressive therapy. Not only can the maintenance therapy possibly work but by treating an even better outcome may be attained than expected. (I think my friend will SVR)
Yes..... I'm sure that you were not trying to be dismissive when in 2 posts you wonder if I had read the article. : )
My intention, despite my apparent gross failure *was* to stay on topic and I'm sorry if you felt that it wasn't. I think it speaks to the type success that we could have seen if the HALT-C "findings" had been different. How many people who needed it most did not treat due to those findings?
best,
Willy
In my friends case, when she attained an RVR full dosing WAS continued. My post spoke to the many people who were deterred by the early findings of the HALT-C trials, and decided to wait for any permutation of maintenance or suppressive therapy. Not only can the maintenance therapy possibly work but by treating an even better outcome may be attained than expected. (I think my friend will SVR)
Yes..... I'm sure that you were not trying to be dismissive when in 2 posts you wonder if I had read the article. : )
My intention, despite my apparent gross failure *was* to stay on topic and I'm sorry if you felt that it wasn't. I think it speaks to the type success that we could have seen if the HALT-C "findings" had been different. How many people who needed it most did not treat due to those findings?
best,
Willy
I understood the article to be primarily about the benefit of low dose pegylated interferon in reducing the incidence of HCC in HCV positive patients.
As I understood your post your friend treated a third time and achieved RVR so I assumed that your friend treated with full dose Peg and ribavirin in hopes of achieving SVR which, according to my understanding, is not "maintenance pegylated interferon".
If I understand correctly she cleared and stayed clear and then went on maintenance treatment - I assume just peg at half dose but that's a guess
I was not trying to be dismissive or denigrate you. I honestly wondered whether you read the article. Maybe I failed to understand your post. Hey, I am happy about it regardless
FLGuy, That struck me too. I wondered whether there were some host characteristics that went unnoticed or undisclosed because you're right - it is counter intuitive that cirrhotic patients did benefit but advanced fibrotic patients did not.
Mike
As I understood your post your friend treated a third time and achieved RVR so I assumed that your friend treated with full dose Peg and ribavirin in hopes of achieving SVR which, according to my understanding, is not "maintenance pegylated interferon".
If I understand correctly she cleared and stayed clear and then went on maintenance treatment - I assume just peg at half dose but that's a guess
I was not trying to be dismissive or denigrate you. I honestly wondered whether you read the article. Maybe I failed to understand your post. Hey, I am happy about it regardless
FLGuy, That struck me too. I wondered whether there were some host characteristics that went unnoticed or undisclosed because you're right - it is counter intuitive that cirrhotic patients did benefit but advanced fibrotic patients did not.
Mike
Hahah. Yes, I *thought* I did, and even thought I understood it. : )
My thoughts were that early HALT-C findings were that maintenance was not effective in preventing increased progression and HCC risk. The new findings that you posted find that maintenance therapy is more effective than earlier thought.
My friends doctor thought that it *could* be beneficial for her, since she was about out of options; why not try? In my friends case, it is too early to claim an SVR, but it looks very good for her.
-----------------------------------
"have come from the same study, the ongoing Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) trial."
----------------------------------
Mike.... the doctor and patient were both trying to try maintenance therapy (although the effectiveness was called into question by early HALT-C findings) to minimize advancement towards cirrhosis and subsequent increased risk of HCC. In the bargain it looks as though they may have also fortunately scored an SVR.
I thought it was germane to your article and post and I still think that it is.
Per the quote in the article;
"During the question session, treatment activist Jules Levin said 4 years ago the initial analysis and strong recommendations not to treat "did a lot of damage to patients and to the field. I took issue with the investigators over that" at the time, Mr. Levin said."
Mike, many people with cirrhosis heeded the studies findings and did not treat. My friend with cirrhosis DID decide to do "maintenance" therapy, or a permutation of it based on the same feeling that Jules Levin had.
I provide one example where there was a happy and unexpected result of this controversial therapy; a possible SVR.
I find it relevant and I'm sorry if you think it out of place.
best,
Willy
My thoughts were that early HALT-C findings were that maintenance was not effective in preventing increased progression and HCC risk. The new findings that you posted find that maintenance therapy is more effective than earlier thought.
My friends doctor thought that it *could* be beneficial for her, since she was about out of options; why not try? In my friends case, it is too early to claim an SVR, but it looks very good for her.
-----------------------------------
"have come from the same study, the ongoing Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) trial."
----------------------------------
Mike.... the doctor and patient were both trying to try maintenance therapy (although the effectiveness was called into question by early HALT-C findings) to minimize advancement towards cirrhosis and subsequent increased risk of HCC. In the bargain it looks as though they may have also fortunately scored an SVR.
I thought it was germane to your article and post and I still think that it is.
Per the quote in the article;
"During the question session, treatment activist Jules Levin said 4 years ago the initial analysis and strong recommendations not to treat "did a lot of damage to patients and to the field. I took issue with the investigators over that" at the time, Mr. Levin said."
Mike, many people with cirrhosis heeded the studies findings and did not treat. My friend with cirrhosis DID decide to do "maintenance" therapy, or a permutation of it based on the same feeling that Jules Levin had.
I provide one example where there was a happy and unexpected result of this controversial therapy; a possible SVR.
I find it relevant and I'm sorry if you think it out of place.
best,
Willy
I remember your post a couple of years ago regarding the use of maintenance use of Peg IFN. I think it was the earlier iteration of this revised study. Up to that point many treatment failure patients here were urged to talk to doc about maintenance. Since then, we have read very few of those kind of suggestions. It's interesting how opinions here sway in the breeze like prarie grass as a result of these kinds of studies.
But I'm struck by one of the quotes:
"Dr. Lok concluded, "Extended follow-up of the HALT-C cohort showed a modest effect of long-term low-dose PegIFN in reducing the incidence of HCC in patients with hepatitis C and cirrhosis, but not in those with advanced fibrosis."
It's further evidence to me of the counterintuitivity of this stupid disease. I would have expected the opposite of that statement to be true.
But I'm struck by one of the quotes:
"Dr. Lok concluded, "Extended follow-up of the HALT-C cohort showed a modest effect of long-term low-dose PegIFN in reducing the incidence of HCC in patients with hepatitis C and cirrhosis, but not in those with advanced fibrosis."
It's further evidence to me of the counterintuitivity of this stupid disease. I would have expected the opposite of that statement to be true.
That is a wonderful story and I am happy for your friend and for you.
I'm not sure how it relates to the posted article though.
Did you read the article?
Mike
I'm not sure how it relates to the posted article though.
Did you read the article?
Mike
I'm glad to see you post this. I have a cirrhotic friend who had failed TX twice. Their doctor seemed to feel that the early results were contentious and urged that she consider maintenance therapy; treat until she cleared, and then continue with half dose TX until new therapies were approved.
This time she exercised, lost weight and took some supplements (milk thistle and vitamin D).
This time, the third time of TX, she hit an RVR and maintained it all the way through her 48 week treatment. She just this week finished TX days ago and we are awaiting the 4 week PCR.
IF her doctor had paid attention to the early HALT-C evidence or "findings", she might have instead been a cirrhotic moving slowly towards decompensation. Instead, she is now within spitting distance of an SVR.
It's great to see the article..... but I am also happy to provide one case history with a happy ending. (and a tip of the hat to Dr. David Nelson of Shands, in Florida.)
Willy
This time she exercised, lost weight and took some supplements (milk thistle and vitamin D).
This time, the third time of TX, she hit an RVR and maintained it all the way through her 48 week treatment. She just this week finished TX days ago and we are awaiting the 4 week PCR.
IF her doctor had paid attention to the early HALT-C evidence or "findings", she might have instead been a cirrhotic moving slowly towards decompensation. Instead, she is now within spitting distance of an SVR.
It's great to see the article..... but I am also happy to provide one case history with a happy ending. (and a tip of the hat to Dr. David Nelson of Shands, in Florida.)
Willy
Have an Answer?
You are reading content posted in the Hepatitis C Community
Learn about this treatable virus.
Getting tested for this viral infection.
3 key steps to getting on treatment.
4 steps to getting on therapy.
What you need to know about Hep C drugs.
How the drugs might affect you.
These tips may up your chances of a cure.
A list of national and international resources and hotlines to help connect you to needed health and medical services.
Herpes sores blister, then burst, scab and heal.
Herpes spreads by oral, vaginal and anal sex.
STIs are the most common cause of genital sores.
Condoms are the most effective way to prevent HIV and STDs.
PrEP is used by people with high risk to prevent HIV infection.
