extended treatment

[Foreign girl]

Hi,

I just came back from my doctor's office (for those who don't know me I am/was 1b, between stages 2 and 3 on my biopsy 3 years ago, high viral load to begin with, 120 IU/ml at 12 weeks, undetectable at 24 weeks).I am on week 39 of Pegasys/Rebetol treatment. I asked my doctor what he thinks about extending treatment beyond 48 weeks and he said it's up to me. He can presribe another 12/24 weeks of treatment at either regular dose or reduced dose. He said that there is no extensive studies done on the benefits of the extended treatment, but the common sense tells him that it may be beneficial to prolong the treatment.

Please let me know any opinions/personal experiences on this subject.

Thank you.

Foreign girl.

[TravisB]

Most of us have heard the claim or theory that whether or not one clears, Interferon has been shown to be beneficial to the liver and some people have experienced a full stage drop in fibrosis after a year of TX.  

When I read about cutting edge stuff whether it's Dr. Cecil or some others, it seems that extending TX is the main thing that these guys do.  

I think it depends on what effects the TX is having on your body.  If you're not anemic or suffering the other blood sides and not severely depressed it might make sense. Another plan would be not to commit yourself mentally  to a certain number of weeks but just do an extra one week at a time and see how you feel.  You might find it easier emotionaly to do it that way.

I asked to do a longer TX after I completed my 24 weeks but I belong to a huge HMO with rules chiseled in stone so they said no.  I think it's great that your doctor is leaving it up to you.   Best of luck. Travsi

[TravisB]

Sorry about mistating your name in the last post.  I've also heard of another variation on the extended TX theme: If someone is not doing well rbc and wbc wise one doctor I read about extends the interferon part of the TX for a while while discontinueing the Riba.

[Foreign girl]

Thank you for your replies. How are you doing? Have you started new treatment yet?

F.G.

[willing]

I'm glad you posted this question - it's been on my mind a lot lately. Along with you and a lot of others on this bus I'm a 1 coming up to that 70% roll of the dice at 48 weeks and wondering whether to push on and if so for how long. I believe I've read extended ranges  from 50 to Mike Simon's heroic 64 in the comments posted here. Obsessive searching (and I do obsess easily) of the medical lit has turned up absolutely no published data to help make this choice. I posted this question on the monitored Hopkins forum but got no response (either the Dr. did not think of it of general interest, or more likely there's no answer yet). I'm trying get a more detailed breakdown of V. Balan's relapse study but all that would show are the characteristics of those who did/did-not relapse at 48.

At the low-level nuts and bolts level, the end-game of treatment remains a mystery. There's lots of tantalising clues but ultimately we don't get it. What happens at end of tx seems to be a replay of what happened at the end of the acute stage of infection  - it has little to do with the meds and a lot to do with the complicated hide-and-seek game the virus plays with our immune response.

Within 12 weeks of when the virus first entered our body our immune system was able to  beat it back down to a very low-level. Then in 20% of people the virus was eradicated and in the rest of us it rebounded and set up permanent housekeeping. Our immune response keeps up  a half-assed attempt at clearing it but all that does is contribute to the build up of scarring. So now the stage is set for a re-enactment, the VL is once again very low, the dice are rolled and ... this time the odds are reversed, only 30% get to "play again".

A very rough approximation based on Balan's data might be that if going from 24-48 weeks reduced relapse from 48% to 28% another 6 months might halve it again. On the other hand there's one line of argument, based on current HIV therapy, that argues that if you depress viral replication enough by meds you're actually undermining the immune response because there's not enough viral antigen around to kick it into action...In short I'm utterly confused, any clues are much appreciated.

[Steve']

Hi there, I think just like TravisB said it really depends on your body & how you have handled the Tx so far, if you feel ok & are not excessively anaemic etc then my feelings would be, "Go For It"....  Good Luck .......

[TravisB]

I'm six months post tx and feeling a whole lot better.  In some ways even better than I was before TX.  No, I haven't started tx and am a long way from doing it again.  I'm pretty doubtful about the chances the second time around especially with what are essentially the same drugs.  That's why I feel that if someone has the opprotunity to extend TX they should strongly consider it especially if they are doing ok with the sides.  

Failing TX means that all the physical and emotional suffering was for nothing.  That's why I figure if someone can put in more time while they are already in TX mode, go for it if possible.  Good luck with your decision. Travis

[MajNeni]

Hi, Foreign Girl,
I agree with Travis.  Think about a 1-week-at-a-time plan.  That way you don't have to feel guilty if you stop, but every week you give it will extend the good probabilities.  Chances are you will be able to carry on for a while longer.  But then keep up the Procrit!
Having had a Riba-vacation, I'm considering going out to 52 weeks.
Maj Neni

[Txangelsaunt]

Hello Everyone,

I just wanted to give my comment about extended treatment. My GI wanted to extend mine for another month. I asked him the pros and cons of this. And he stated that there was nothing miraculous about extending. So I asked him to end treatment at 48 weeks. I (Was)A 1A. And am undectable thus far.

Thanks for listening,

Txangelsaunt

[Ambush]

When did you first show undetectable?  I am concerned because I was not clear at 12 weeks (1A) dropped from 576,000 to 6,160, so am starting to toss this extended tx idea around in my head.
ambush :)

[willing]

on an emotonal level, I'd find open-ended tx duration pretty hard to live with. How long do you go on ? and why ? So far I've found the milestones and countdown a big help in getting through the rough times ( get to week 12, then to half-way, then start a countdown..). Just going on as long as you can possibly stand it  with no idea of whether it's doing you any good may be  a good strategy but I'm having a hard time accepting it..

[Indiana]

I have read some stuff about extending tx and the info is pretty sketchy at best. There have been some small studies awhile back that seemed to show that extending tx out to 52 weeks had some benefits but beyond that the risks outweighed the benefits.
In the last year or so I have watched as many doctors have started to take the type 2's and 3's out to 48 weeks instead of 24. It's not the "standard" yet but it appears to be heading that way.
The latest "cutting edge" stuff I read seems to show a new wave of thought that hinges on exactly WHEN you clear and then doing tx for 48 weeks from then.
There is always that little problem with the possible long term toxic effects that the meds can have on us. We ride on the edge when we take these drugs at the levels we need to to kill the virus for an extended time.
I looked at all this myself and decided to do 50 weeks. That was just how my refills worked out. I was looking at a little longer time but I really never considered doing more than 52 weeks. That seemed to balance my desire to give myself the best odds I could but still not take a big chance on having the meds do permanent damage. That was ME. And it worked...for ME. My starting load was not high and all I know is I was clear at 24 weeks....never had a 12 week test.
I like the idea of going a bit longer for type 1's.....but not too much longer. That's just MY thinking.
You have to work this out in your own head and do what you think is right for YOU.
Best of luck whatever you decide.

[TravisB]

One thing I said to foreign girl is not to make it open ended but do one extra week at a time.  When you're running it's not good to think about mile ten but rather grind out one mile at a time.  That's how I am but everyone is different.  

I wanted to do TX longer because I didn't clear at week 12.  Had I cleared at week 12 I probably wouldn't have asked to do more. I tested clear at the end of TX but relapsed 2 months later.

I'm actually not that much of a propenent for TX but I think that once on it, you should do as much as you can to make it a one time thing.  This all depends on how you are handling it.  To me the two main questions are when did you clear and how are you doing in mind and body.  The numbers are not that much better for those that go longer but they sure as hell are not worse.

[Revenire]

I understand in Europe the standard length of tx for 1s is 52 weeks; this was approved by the European Commission. I don't know what they based it on but that's the scoop.

My doctor is considering extending my own tx past the 48 week mark. I would go 52 IF he could point out some evidence this would aid in SVR. I am also worried about the long term effects of the drugs we're all taking.

[willing]

thanks for the feedback - if you happen to come across any of the links/references that talk about >48 week therapy please post them: I'm sure they'll be of great interest to all of us trying to pick the magic number.

[Dirac]

I want to share with you my experience with trying
treatment extension. I am in the last month of
treatment and asked my doctor to extend the treatment
for one month more to increase my odds.
He did not like the idea and
mentioned something about me being on Neupogen since week #5,
and it would look a bad decision if I get infected in
this extra month. My feeling was, well, I did not have
such problem in 48 weeks so it is a good chance not
to have such infection in these extra four weeks. But
I said to myself, he is the doctor and he must know better
and I decided to follow his instructions and will not take
that strong medicine for more than 48 weeks.
I wish you all the best of luck.

[Dirac]

I have to add some points:
(1) I was "undetectable" at the first test in week #12
the test was <615 and I had the same result at week #24.
(2) My genotype is most probably 4 which has a better
chance of 67% compared to the 50% of type 1:
http://www.pslgroup.com/dg/222676.htm
(3) My side effects have been minimal except for the
wbc drop that I take Neupogen for.

[Micro2]

Hello All, After 48 weeks of Peg-Intron and Riba, My viral load has decreased from 857000 to 15. Hmmmm... My GI wanted me to go on Infergen and Riba for 1 more yr but ,when he sent me to a Hepatologist for a second opinon, the Hepatologist said no. He said NO Riba after 52wks due to unknown permanant side effects and NO infergen because I am not cirrhosed. A new heptimax has revealed that my count has risen to 75. They said "not to worry".
I am still on Peg-Intron at 52wks and have stopped the Riba. A new heptimax was drawn yesterday and I am told if its up...then we will start Pegysis...if its the same or down...we will stay on Peg-Intron at a reduced maintenance type dose to prevent breakthrough. BTW I am 48-1b-stage 1-grade1 and other blood tests are looking good. Any thoughts ? GIPA?

[Revenire]

I found the press release on the 12 month treatment but no studies to back up the reasoning for the extra month of tx. The Committee for Proprietary Medicinal Products, I believe this is the supra-European health body, was the agency to make this recommendation.

Interestingly, they are no longer recommending a biopsy.

-------------------------------------------------

Date:  July 18,2003
Sender Name:  PR Newswire

European Commission recognises Roche's pivotal trial in new PEGASYS label for Hepatitis C  
  
Basel, Switzerland, July 18 /PRNewswire/ --

- Label changes set to benefit patients as it relates treatment
recommendations to viral genotype

Roche announced today that the European Commission has approved a new label for PEGASYS (peginterferon alfa 2-a (40KD)) in Europe, as a result of Roche's pivotal study(i) that  demonstrates that the duration of combination therapy and dose of Copegus (ribavirin) for chronic hepatitis C patients depends on viral genotype. This decision is set to benefit patients as they will only continue on therapy for as long as needed to obtain benefit, depending on genotype.

The EC recommends that patients infected with genotype 1 should receive 12 MONTHS OF THERAPY with standard dose Copegus (ribavirin), while patients with genotype 2/3 only need 6 months of therapy and a lower dose of Copegus. The decision was based on the unanimous positive opinion adopted by the Committee for Proprietary Medicinal Products on 24 April 2003.

"We are pleased that the European Commission has approved the label to reflect this new and important data on how best to treat hepatitis C patients who are prescribed PEGASYS and Copegus," said William M Burns, Head of Roche's Pharmaceutical Division. "It's not only a competitive label but one that provides benefits to patients. "

Another change to the label is that PEGASYS combination therapy NO LONGER REQUIRES A PATIENT TO HAVE A BIOPSY confirming the extent of liver disease prior to starting treatment. This is particularly helpful to patients. PEGASYS combination treatment is also the only pegylated interferon hepatitis C treatment in Europe that is indicated for patients with compensated cirrhosis, an advanced stage of liver disease that can lead to liver cancer and the need for liver transplantation.

Excellent Treatment Outcomes

The clinical results examined by the Committee demonstrate that PEGASYS, when combined with Copegus, provides some of the highest sustained virological responses (SVR) ever seen in chronic hepatitis C. New SVR rates included in the label include several firsts.

* Overall, up to 63% of hepatitis C patients treated with PEGASYS combination therapy achieve a SVR - the highest virological response rate included in a European label.

* For PEGASYS patients infected with genotype 1, that is the most common yet one of the most difficult-to-treat genotypes, 52% of patients achieved a SVR - the highest response included in a label for a hepatitis C treatment in Europe.

* For PEGASYS patients infected with the genotype 2/3 viruses, 80% of patients achieved a SVR when treated for 24 weeks and a low daily dose of 800 mg of Copegus.

PEGASYS is the only pegylated interferon with which prospective research has been undertaken that provides for the customisation of therapy according to genotype, and has had the data reviewed and accepted by regulatory authorities. In fact, this seminal research has now been reflected in the US NIH Consensus Conference on the Management of Hepatitis C and it is affirmation of the importance of genotype. A patient's genotype is the most important factor influencing the outcome of treatment.

Roche in Hepatitis

Roche is committed to the viral hepatitis disease area, having first introduced Roferon-A for hepatitis B and then C, followed by PEGASYS in hepatitis C. PEGASYS is also in phase III clinical development for patients infected with the HBV virus. Roche manufactures and sells the Amplicor HCV Test (v2.0) and the Amplicor HCV Monitor Test (v2.0) - two tests used to detect and quantitate the amount of HCV RNA in a person's blood. The company's commitment to hepatitis is further reinforced by the in-licensing of Levovirin, an alternative antiviral. Levovirin will be studied with the objective of demonstrating superior tolerability over the current standard, ribavirin.

About Roche

Headquartered in Basel, Switzerland, Roche is one of the world's leading innovation-driven healthcare groups. Its core businesses are pharmaceuticals and diagnostics. Roche is number one in the global diagnostics market, the leading supplier of pharmaceuticals for cancer and a leader in virology and transplantation. As a supplier of products and services for the prevention, diagnosis and treatment of disease, the Group contributes on a broad range of fronts to improving people's health and quality of life. Roche employs roughly 62,000 people in 150 countries. The Group has alliances and research and development agreements with numerous partners, including majority ownership interests in Genentech and Chugai.

All trademarks used or mentioned in this release are legally protected.

Notes to the editor:

* PEGASYS was first approved in European Union, just over one year ago, on June 20th, 2002.

* PEGASYS and Copegus have now been approved in over 80 countries, with the latest approval in Australia in June, 2003.

* A SVR denotes that a patient has remained viral negative six months after completing therapy and is considered virus free or 'cured'.

* A biopsy is used to confirm the extent of liver damage (fibrosis).

(i) Hadziyannis, S. et al. "Peginterferon Alfa-2A (40 KD) (PEGASYS) in Combination with Ribavirin ): Efficacy and Safety Results from a Phase III, Randomised, Double-Blind, Multicentre Study Examining Effect of Duration of Treatment and RBV Dose". EASL, 2002.

Contact: Sheila Gies, Roche, [phone] (mobile), Alison Thorpe,
Burson-Marsteller [phone]

[Southernboy]

Hi micro2,

Read your post and just had to comment as I am in a similar situation.  I think your original doc might be on the right track and the Hepatologist you used for a second opinion is....well lets just say you should get another opinion.  

Use of Infergen in tx has nothing to do with the presence of cirrhosis.  It is being pushed as an alternative to the interferon alfa 2a or 2b in cases of relapse or nonresponse.  Its only downside is that it is not available in a peg form so must be injected on a more then 1x per week basis.  This can cause more severe side effects so this drug has been pushed into the backround.  They are working on a peg version.  

In addition, there are no studies showing that use of ribavirin for more then 52 weeks leads to any increase in adverse side effects.  In fact, NIDDK is at present sponsoring a study that will treat patients, who cannot tolerate interferon, with long term doses of ribavirin monotherapy.   Supposed to last 4 years and is a phase IV study.  Look at www.clinicaltrials.gov for more info.

Hope this helps and will be glad to share any other info I come up with with you.

Best to you and hope you are feeling well,
Steve

[willing]

you guys might be interested in the following small, recent study that combined high dosage IFN on an induction schedule+riba with extended  (76-week) <a href="http://www.blackwell-synergy.com/openurl?genre=article&sid=nlm:pubmed&issn=1352-0504&date=2003&volume=10&issue=3&spage=205">duration</a>. The results, in high response and low relapse are pretty encouraging - on the other hand 6/24 patients had to be hospitalized...

The hepatologist may simply have been saying that with a  fibrosis score of 1 there's no reason to undergo such dramatic, unproven,therapy - even at 48. Best wishes.

[Helyn]

I have been undergoing treatment for almost 10 months now and after reading other sites, stick only to this one.  I am a lurker - a term I first heard here.  I have laughed and cried with you and appreciated all of the information more than I can say.  No one other than my husband knows about my illness.  I have worked every day and collapsed almost every evening and weekend.  I have met all of my other responsibilities to family, friends and work.  I haven't cleaned my house much, that's for sure.  The thing I wanted to add is that in all the time I have been reading the "flow" of the questions, other than from new folks, seems to be from people who have not cleared the virus, and questions about "what now".  I have to say that is where I am now, having learned last week that I did not clear and hearing what the alternatives are.  I am someone who likes choices and likes to have some control, but honestly, some of these decisions (like switching to Pegasys, or Infergen-be it three times weekly or daily, or doubling up on Peg, or going over 1200 mg of Rib, or quitting and seeing what happens, or doing one or another until Infergen is peglated (sp?)) - are just a bit overwhelming for me.  I consider myself to be somewhat of an "expert" lay person, having read almost all I can stand, but geez, we aren't physicians, we aren't chemists, we are however unfortunate enough to have a disease that is in its infancy in terms of treatment.  I'm sorry to go on but I am being faced with, "here are some options" - and my favorite question - "What do YOU want to do?"  Well, I'd like to stop the madness quite frankly, grow some of my hair back, get my wonderful sex life back, and stop all the associated irritations and infections and many, many medications to deal with them.  But I want to fight the good fight too.  I guess I'm just a bit sad and feeling like I've failed, though I did everything I was supposed to do.  When I read someone say that when you don't clear, you have gone through treatment for nothing, I could cry.  Anyway, after so long reading about all of you, and sending you my love and support in my own way, I thought I'd log on and maybe get some support myself.  Thanks.

[Southernboy]

Hi,

Thanks for the link willing, very interesting.  Also, you could be right and as a stage 1 micro2 could be better served by waiting for more proof or other treatments, although, almost having the dragon beat, one just wants to see if the scales can be tipped just a little further....!  I tend to judge by me, aggressive by nature and a late stage 3 who was very symptomatic even before starting tx.  I look at things differently and feel I need to be very aggressive now to get my life back.

Most of my ranting is because of feelings very well expressed by helyn in the previous post.  I feel for you helyn and understand your disappointment, frustration, anger and saddness.  Wish there was more I could do to help.  There are many people on this site who are full of knowledge and many others who are full of support.  By reaching out, I am sure they will come to you and provide info and a shoulder to lean on.

Hope both of you are well as you can be,

Steve

[Revenire]

I received this email from the HEPATITIS DOCTOR himself today. The fellow who does not follow the cookie-cutter approach to tx and he said:

"With severe fibrosis (stage 3) longer treatment is attractive to me. If you can go longer I think it will improve your chances of cure."

I discuss with my doctor to go 52 weeks (he has already talked about me going a bit longer), or longer, depending on the pros and cons ... meaning the long-term damage these drugs could be doing to me vs. improved odds of SVR.

Take care all!

[willing]

welcome - thanks for writing. You certainly  haven't gone through the treatment for nothing (the whole notion of "maintenance therapy" is built around the benefit the drugs have in the absence of clearance). Working so hard at something and having it not work out can only hurt - and only time can heal that. You had the courage to try and the perseverance to get this far -  those strengths will be with you as you plan your next move. Fabienne's comment to dtr's thread back on 8/18 is a good reminder that wise acceptance can be another important strength in getting through all this. No matter how bad the sides get, I think you're at the most difficult part of the journey. Thinking of you.

[Tim in Tenn]

I am also stage3 grade 2 geno 1.Have been reading that geno 1's with high viral loads(mine is 5,190,000)are more likely to be non-responders.Also in my case,my gastro said my bloodwork was all normal(except viral load)so he didn't think I would have serious liver damage.He even asked just before biopsy if I wanted to reconsider having it done,and then even after the bx he said the tissue was healthy looking.Then when I got the bx results it wasn,t good.So given these circumstances shouldn,t it be standard that all persons hepc positive have biopsy as soon as possible.

[Revenire]

I can't comment on the biospy question. I just posted what the press release said.

Common sense tells me a biopsy is needed to show extent of liver damage but somehow this European medical body came to a different conclusion. I wish I knew their reasoning. I would hazard a guess this body is made up of European medical experts right? I would like to read exactly what they said.

That said, my ultrasound showed the liver to be "normal" but the biopsy showed Stage 3.

New, non-intrusive tests are coming that can also show the amount of fibrosis. I believe Fibrospect is one. Tx is now thought to be able to reverse fibrosis; studies are ongoing to prove this -- I think.

Anyway, I found this European approach interesting and would like to know more.

Take care,

Scott

[harley dude]

I'm geno 2b stage 3 fibrosis, when I first heard my geno type the nurse called and said my GI will treat for 24 weeks, I was thrilled, the next visit with GI, he suggested posibbly 48, if I was cleared at 24 weeks it would be my choice, at first I said I would not go a day past 24 weeks, well as months went by and I started feeling normal, and reading all of you'll posts about going longer, I'm now considering going 48 weeks if I continue to feel like I'm feeling now, sure hope I'm making the right choice, seems like no one is positively certain going longer than 24 weeks for geno 2b is worth it. -- HD

[Revenire]

Yeah, well I am going to go for the extra weeks/months if I can handle it. I've decided that.

I'd like to do this tx just once.

If my doctor, who is a big mucky muck when it comes to treating HCV and liver disease says "we don't need to" then I may not push to have the extra fun of another month or longer.

I want this **** out of me ... I want to kill it. You know the feeling I am sure.

[AK - Hepper]

I asked my doc about this last week, he said: " Most people are so exhausted by the end of 48 weeks they just want to quit, but if you still feel up to it and no major complications, I don't see a problem with doing a little extra mop up." I thought that was a pretty good way of putting it.

[Indiana]

****....I just HATE it when I hear a story like yours. I feel SO bad for you.
I am one of the "lucky" ones who managed to clear as a type 1b. We type 1's who succeed don't post actual questions much. I think this is because we are on this stuff SOOO long that we pretty much understand most of it by the time we're 1/2 way through. As long as our numbers look reasonable we just plod along and answer questions as best we can.
I spent most of 3 years getting ready to treat this and another year doing my tx. I studied this stuff every day. I read everything I could find on it and since there is NO real consensus amongst the medical people on this stuff I was forced to come to my own conclusions a lot. So, I know how frustrated you must feel.
There is NO doctor anywhere who can say they really KNOW what all the answers are. For those who do not succeed the firat time it gets even harder to guess at the right answers. But it's still all a big guess. Now the newer meds are making the decisions even harder.
A lot of the decisions depend on what your numbers were all the way through this. Your age, genotype, damage levels, and just how you responded to your tx makes a difference. I assume you were doing the Peg/Intron and were probably a type 1 after 10 months. I thought a little about what I would do if I failed and made some decisions before I finished. I decided that since Pegasys and Peg/Intron were so similar there would be no advantage to just doing "standard" tx with that as it would probably not make a difference. But the sides are so much better with Pegasys I would consider a more agressive tx with that. That Peg/Intron kicked my butt so badly I don't think I would do THAT again. The Infergen is a "consensus" interferon(man-made) so it is very different from both of the other Peg interferons. They have had some limited success with it on those who failed Peg tx. Better success on relapsers than non-responders. They expect to have a Peg version of it in about a year or so.
So, if your damage is at the point where you HAVE to do something I think you are looking at getting SUPER agressive with the Peg treatments or looking at the Infergen with Riba. If you can wait for the peg version you would be better off.
I really think an even better plan would be to find a study using a protease inhibitor and join it. I think that will be the real success story for all this in a few years. I guess it depends on where you live.
I know that Dr. Cecil treats many "hard to treat" people and has a fairly unique approach using his own theories with one of the 2 Peg drugs. He does answer his E-mails. Maybe you could query him with your particulars and see what he says.
I know...more choices......
You have NOT done all this in vain though. There is good evidence that you have probably significantly improved the condition of your liver while on tx. This improvement is independent of wether or not you succeed at tx. Most show some improvement and many show MAJOR improvement. Especially those who do more than 24 weeks. At least you can get some comfort in that fact.
Get yourself clear of your current meds and get your brain straight. Then look at your choices and "pick your poison".
I sure hope you find SOMETHING that works for you.
Best of luck.............

[BobK]

I stopped by and this thread caught my eye for good reasons!  I did 100 continuous weeks of peg-intron and ribavirin at full dose.  My treatment plan evolved as the data from my bloodwork came in.  My initial response to the meds was a greater than two log decrease in HCV viral load within three weeks of initiating treatment.  After that the secondary phase of viral elimination was very slowwwww (based on monthly PCR).  I did test non-detect at 24 weeks and my docotor told me we would treat for 12 months after that point.  I plodded along living from PCR to PCR, they were monthly but we switched to every three months after the non-detect test.  After the 18 months were over I still had enough meds, which I had purchased earlier prior to changes in my insurance coverage, to treat for an additional six months. Wishing to only go through treatment once we decided to keep going.  I was also very stable as far as blood work goes....crappy values but stable I will say that the second 50 weeks was the hardest!

There were other aspects of my profile which contributed to my decision to treat longer.  One of those was the extent of liver damage which was significant.  The other was that I probably would not be in the position to have affordable access to the meds for this length of time in the future.  The biggest was that from the secondary elimination phase it seemed fairly obvious that I was a likely relapser so I decided for longer treatment to aid in any healing or reversal of fibrosis I could obtain as well as hoping to increase my chances of SVR.  Interferon is still the most efficacious anti-fibrotic that we have available and it will be interesting to see how the COPILOT and HALTC trials turn out.  I will find out the extent of healing (or not) that took place during the treatment process when I am re-biopsied on SEpt. 10.

I did relapse, which did not suprise me...disappoint yes but suprise no, and my doc and I are currently putting together a "what do we do now" program.  I am currently taking vit E and ursodeoxycholic acid in an attempt to minimize regression of any gains achieved during treatment.  I am also taking a version of Sho-saiko-to which has other antioxidants as well...all with my docs agreement.  As of now the only thing I can say is that my liver panels have normalized after rising upon relapse. It did take me about 5 months to completely recover from treatment which seems normative regardless of length of treatment and I must say that from a subjective viewpoint I am feeling better than I have in many many years.  So all-in-all I was disapointed in not achieving SVR but I am VERY grateful to be feeling as well as I am when I look back and see how badly I felt and the high level of impact HCV was having on my life.

Although data on longer treatment is sketchy at best there are only a couple of things that can be done to improve the chances of the patient with a poor treatmetn profile.  Extended treatment and higher doses of INF are about the only options left for us. There is no doubt in my mind that longer treatment will prove beneficial for some....how many "somes" is the big questions that needs to be evaluated to judge the benefit vs risks of such a program.  I think in the short-term the treatment of 2' & 3's who show a slower response time will be much improved to a extended treatmetn, i.e. 48 vs 24 weeks of treatment...for us 1's the data may be a little slower coming in so for now we each will have to cross that bridge when we come to it.

kind regards,
BobK

[Southernboy]

Thanks for the post.  For me it was a great pick me up in both info and attitude.  Sorry that after your heroic effort you did not quite reach the holy grail but I hope the improvement in your liver is a really great one.

We all have a lot to learn don't we?  Wouldn't have been my first choice but....does no good complaining about your cards.

Glad you are feeling better and hope this continues.

Steve

[willing]

thanks for sharing your story - like Steve I found it a useful lesson in strategy and in attitude. I'm puzzled about what led you to suspect you might relapse : you had a 2-log drop by the 12th week and were undetectable by the 24th thus meeting the standard profile of a  "responder". How high were your baseline and 12th week VL? Anyway,congratulations on a remarkable battle and best wishes on your upcoming biopsy.

[Revenire]

Bob, thanks for the information.

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Hepatitis C 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 maintenace therapy.

Mitch 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 ± 15.6), log HCV-RNA titer (5.85 ± 0.15 copies/mL), histology score (9.5 ± 0.2), and percentage with cirrhosis (25%). After 6 months of treatment, significant reductions (P < 0.05) in serum ALT level (62.6 ±  9.6), log HCV-RNA titer (4.79 ± 0.13 copies/mL), and hepatic inflammation (4.0 ± 0.2) were observed. These improvements were maintained in the patients randomized to continue interferon. Stopping treatment was associated with an increase in serum ALT, log HCV-RNA, and hepatic inflammation back to baseline. After 30 months of treatment, mean fibrosis score declined from 2.5 to 1.7 and 80% of patients had histological improvement (P < 0.03). Discontinuation of interferon was associated with an increase in

mean fibrosis score from 2.2 to 2.4 and worsening of hepatic histology in 30% of patients (P < 0.01). Shiffman concluded that these data support the hypothesis that maintenance interferon may prevent histological progression of chronic HCV in patients who remain viremic.

I think there are some doubters that maintenance therapy will prove for all non-responders to be significantly meaningful, particularly enough to suffer the rigors of ongoing long-term therapy. But these two studies will hopefully answer this question. One concern that has been raised is that complete non-responders or individuals with less virological response than others may not benefit much if at all from long-term low-dose interferon maintenace therapy.

THE TWO STUDIES

There are two main differences between these two studies. In one study, a person receives the Hoffman-LaRoche Pegasys pegylated interferon, and if not virologically responsive is randomized to low dose maintenance Pegasys interferon or no therapy at all. In the other study, a participant receives low dose Schering-Plough Peg-Intron pegylated interferon, and if not responsive virologically is randomized to low dose maintenance Peg-Intron interferon or colchecine (described below)..

HALT-C  Hepatitis C Antiviral Long Term Treatment Against Cirrhosis

This study is being conducted by the NIH (National Institutes of Health) and will be available at 10 sites listed below. The study size is targeted for 1300 people. Essentially, the study is for people with cirrhosis or more advanced disease who might progress to cirrhosis. The goal of the study is to see if a progression from fibrosis to cirrhosis can be prevented or delayed, and to see if progression from cirrhosis to decompensation can be delayed or prevented. You can enter the study with frank cirrhosis. Eligibility criteria -- for individuals with detectable HCV viral load and previously treated with at least 12 weeks with any form of interferon or interferon/ribavirin; a person will need a fibrosis score of 3 (Ishak Fibrosis Scoring System - range 0-6). Study participants will receive 5 months of full dose Pegasys 180 ug/ml once weekly subcutaneous injection (Roche pegylated interferon) + ribavirin. After 5 months of treatment, if a person has detectable viral load they will be randomized to low dose interferon alone (90 ug/ml once weekly subc. injection) or no treatment at all. Participants will receive 90 ug/ml for 3.5 years. Biopsies will be performed at baseline and at 2 and 4 years into the study.

A biopsy performed within 12 months prior to start of study is acceptable. A full battery of bloodwork will be performed at baseline and throughout the study including monitoring histology changes, and regular bloodwork monitoring including ALT and HIV-RNA. Individuals with HIV or hepatitis B are not eligible for the study. Additional eligibility criteria: hemoglobin „11 g/dL; neutrophil count>1,500/mm3; platelets >75,000/mm3.

STUDY SITES LISTED BELOW.

COPILOT Study--Colchecine Peg Intron Long Term Therapy

This is a study of maintenance Schering-Plough's Pegylated Intron therapy at a dose of 0.5 mcg/kg (once weekly subcutaneous injection). There will be 100 study sites, and 17 sites are up and running now. About 1000 participants are planned for enrollment. Participants will be randomized to either colchecine (0.6 mg twice daily), which is a pill, or Peg Intron. The study will look to see if long term Peg-Intron will prevent the clinical progression of disease and fibrosis in patients with advanced fibrosis or cirrhosis secondary to hepatitis C, who are virological non-responders to interferon/ribavirin. More specifically, the study will evaluate the effect of colchecine and Peg-Intron on the slowing or preventing of fibrosis progression, progression to decompensation, and progression to liver cancer. The study is 4 years in length. The hope for maintenance therapy is that individuals who are complete non-responders, partial responders or relapsers to prior HCV therapy will be able to slow or prevent fibrosis progression and HCV disease. The goal is to keep people alive and healthy enough to receive additional treatments for HCV which are in early stages of  research and development.

This study is designed for individuals who have severe fibrosis or cirrhosis and have tried more than one attempt at therapy and were unable to achieve undetectable HCV-RNA. Colchecine is an anti-fibrotic drug. In alcoholic hepattis and cirrhosis, colchicine has shown a survival benefit.

In alcoholic hepatitis interferon, therapy is not indicated because interferon is an antiviral, and in alcoholic hepatitis fibrosis is due to damage from alcohol. The efficacy of colchecine is unknown in HCV. There will baseline evaluation by biopsy, serum fibrosis markers, liver cancer markers, ultrasound to look for tumors in the liver, and alpha-fetoprotein (marker for cancer). For patients with cirrhosis the study protocol calls for clinical follow-up during the study for cancer by ultrasound examination and alpha-feotprotein measurement. The study will evaluate if treatment for individuals who are expected to progress to liver cancer or decompensation with 2-5 years can delay or prevent progression. Certainly, preventing progression is a main goal, but reducing progression rates would permit a person to avail themselves of new treatment developments that may emerge in the future. Compliance will be assessed and monitored by study coordinators, monthly phone calls and at regular visits.

If you think you might be intertested in this study please make sure your doctor checks the protocol to make sure it's appropriate for you. The use of herbal/alternative treatments except those listed below will be strongly discouraged: multivitamins without iron, thiamine, vitamin E, and folic acid.

People with liver failure and decompensation, or HIV are excluded. But individuals with advanced fibrosis and cirrhosis are eligible for the study. Other inclusion criteria include: hemoglobin „11 g/dL in males or „10 in females; neutrophil count>1,500/mm3; platelets >70,000/mm3; fasting blood sugar £115 mg/dl or within 20% of the upper limit of normal for non-diabetics; alpha-fetprotein within the normal range or < 100 ng/ml with normal ultrasound; ultrasound with no evidence of suggested hepatoma.

The Principal Investigator for this study is Nezam Afdhal, MD. He is Associate Prefessor of Medicine at Harvard University School of Medicine, Chief of Hepatology, Beth-Israel Deaconess Medical Center.

SITES FOR TWO STUDIES
HALT-C (physicians call requested)

University of Massachusetts in Worcester
Herbert Bonkovsky, MD  508-856-3068

St. Louis University in Missouri
Adrian Di Bisceglie, MD  314-577-8762

Massachusetts General Hospital in Boston
Jules Dienstag, MD  617-726-7450

University of Colorado Health Sciences Center in Denver  Gregory T.Everson, MD  303-372-8862

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Liver Disease Section

Marc Ghany, MD 301-402-5115

University of California at Irvine in Orange, California
John Hoefs, MD 714-456-7518

University of Texas Southwestern Medical Center in Dallas
William M. Lee, MD 214-648-3323

University of Southern California in Los Angeles
Karen L. Lindsay, MD 323-442-5550

University of Michigan in Ann Arbor
Anna Lok, MD 877-452-4813

Medical College of Virginia Commonwealth University (physicians call) Mitchell L. Shiffman, MD  804-828-4060

COPILOT

Since there will be 100 sites the list is too long to reproduce here. You can call the main study site: Jocelyn Leone, the study coordinator and nurse practitioner for a site in your area (617 632-1071). There are sites in all major cities.  Below are sites in some major cities.   The list is  in no particular order.

Nezam Afdhal, MD (Beth Israel Deaconess Medical Center)
Boston, MA
617 632-1071

David Nunes, MD (Boston Med Ctr)
Boston, MA
617 638-8221

N.Y. Presbyterian (Bob Brown, MD)
New York, NY
212 305-0662

North Shore University Hospital
Div. of GI
Manhasset, NY
516 562-4281

Sam Moskowitz, MD
Forest Hills, NY
718 520-0857

Doug Dieterich
New York, NY
212 995-6930

Edward Lebovics, MD (NY Medical College)
Valhalla, NY
914 493-7337

Murray Ehrinpreis, MD (Haper Hosp)
Detroit, MI
313 745-8601

Viktor Eysselein, MD (Harbor-UCLA Med Ctr)
Torrance, CA
310 222-2474

Robert Gish, MD
San Francisco, CA
415 202-1530

John Goff, MD
Denver, CO
303 573-9951

Rajeev Jain, MD
Dallas, TX
214 979-0883

Paul Lebovitz, MD
Pittsburgh, PA
412 359-6950

Pierre Nader, MD
Seattle, WA
206-243-4940

George Nikias, MD (Hackensack University Med Ctr)
Hackensack, NJ
201 996-3196

Eddie Chueng, MD
Oakland, CA
510 654-5555

Mitchell Davis, MD
West Palm Beach, FL
561 845-6228

Mark Swaim, MD (Duke Univ  Med Ctr)
Durham, NC
919 403-5228

John Venetos, MD
Chicago, Ill
773 489-6262

Paul Thuluvath, MD (Johns Hopkins Hosp)
Baltimore, MD
410 614-5389

Ira Jacobson, MD
Cornell Hospital, Chief of GI
New York, NY
212 746-2115

[BobK]

The HALTC studies closed back in March or April of this year.  I don't know about the COPILOT studies but I imagine they are also closed although I don't know for sure.  

Data accumulated from other studies which have been completed show that about 68% of people have no reversal of fibrosis, 24 % show improvement and 8% actually have worse histology upon completion of the treatment.  This was all released after I finished treatment.

I felt I was going to be a relapser by looking at my viral elimination data.  Since I had monthly PCR I could see that the slope of that curve was very shallow....not a good sign for SVR!  I also had all the negative factors, significant fibrosis, length of having the disease, male, not clear at 12 weeks, high initial viral load ect.  It was obvious  that although my body was responding that it was going to be very difficult for me to achieve SVR....extended treatment was the only chance for me and at that time there was information indicating that more patients responded histologically.  I think my viral load at 12 weeks was around 100,000 copies/ml.  Starting load was 10-15 million depending on which PCR you want to use..these were both bDNA test which always seem to overestimate the actual viral load.  I can find the actual numbers if it is important but the numbers I reported are pretty cloe to the "actual" numbers.

I am comfortable with the outcome since it didn't really suprise me.  I and my doc are waiting until the some data on the gamma interferon trial comes in and also considering the REPEAT trial which is in the making.  This trial is for people who relapsed after treatment with peg-intron and they will be treated with pegasys and copegus.  If not clear at 24 weeks will be assigned to maintenence dosing.

kind regards,
BobK

[Helyn]

Thank you so much for your thoughts about the realities of making choices as a non-responder in a world where the treatment of this disease may be progressing, but where there is still so many unknowns.  I had a good friend who, for reasons other than hep, had three unsuccessful kidney transplants and in one of her more energetic moments, she actually made a "Wheel of Fortune" spinning device out of cardboard and put it on her hospital door for the surgeons who came in every day to monitor her cyclosporin levels.  She knew that so little was really known about dosing that she would invite them to "spin the wheel" to determine her daily amount.  Sometimes that's what I feel like in making a decision about what to continue with.  I have decided to start Pegasys and will begin this coming Friday.  As a result of this forum, I will be asking if I should be doing an increased dose of it beyond what has been prescribed.  I just wanted to add that I have just spent the first glorious weekend I have had in almost a year, without any new doses of either drug in my system (though I'm still on Aranesp) and I got so much done I almost felt like my old self!!!  And I had great sex with my husband to boot!!!  Makes me realize that I don't want to stay off this horrible medicine any longer becasue if I did, I'm not sure I could go back.  I still feel crappy enough that I could get back on it this week and the feelings would be familiar.  Now that's pretty crazy, ain't it?!  Anyway, I hope everyone had a good long weekend.  I do really appreciate this forum and consider it my support group.  Thanks again!

[willing]

Hi, I hate to suggest this after you had such a great weekend but if you're gearing up for another battle you might be interestd in the following <a href="http://www.hivandhepatitis.com/hep_c/news/070703a.html">clinical trial</a> from Roche. I know, 72-weeks, that much fun should be illegal.

[Foreign girl]

Thank you for all of your very informative responses. I still have not decided whether I want to continue with treatment beyond 48 weeks. I will let you know about my decision.

F.G.

[Helyn]

Thanks for the information and link.  I'll call my doc about it tomorrow and try to get some info before I start Pegasys on Friday.  72 weeks - hard to wrap oneself around that one.  What exactly is "an induction program"?  My understanding is that it is a higher dose of a drug to begin with (but how long and how much), tapering to a lower dose to be maintained throughout the rest of the treatment. Thanks again!