Am I a non-responder?

[sunshines76]

Hello! Got diagnosed with HCV, genotype 1b two years ago. Looks like I've had it for at least 30 years now - had a blood transfusion in 1970s... I am now on week 14 of TX (pegasys + ribavirin). Don't feel any side effects at all, except for some mild hair shedding. I also drink plenty of water, and feel very good, actually better than before the therapy. Got more energy. Yet, my PCR test results are ... a buzz killer:
- 3 weeks before therapy- 280,000
- 1 week before therapy - 1,060,000
- week 4 of therapy - 13,000
- week 8 on therapy - 2,575
- week 12 on therapy - 66,742
- week 13 on therapy - 103,000

Looks like a roller-coaster ride to me... Am I a non-responder? My doc is suggesting keep on the current meds will week 24 and then if the virus is still detectable, switch me on infergen.

I am still hopeful... but my optimism is kind of down now when I got my labs done for week 12...

Anyone had the same happen to them as far as viral load climbing up? Is pegasys not working for me?

[Bill1954]

This appears to be a classic case of non response, alright. I suppose given that you tolerate treatment so well, you might explore further response until week 24; but to be honest the odds of you actually succeeding in achieving sustained response are minuscule at this point. You did not achieve a 2 log 10 reduction in viral load at the 12 week juncture; and projecting your viral response now leaves a very gloomy picture. A two log reduction using the baseline load of 1,060,000 would have been 10,600 IU/mL. Although you did achieve that figure earlier in treatment, it appears you have suffered viral breakthrough of sorts. The doctor suggests continuing until W24; you might ask him his reasoning behind this?

If you have little fibrosis at this point, it is probably a much better idea to forgo any further treatment until the new PI drugs arrive out of clinical trial… right now that looks as though it might be as early as mid 2011. At that point, you can take another look and see what the advertised SVR rates are; as well as the treatment duration. Right now, the clinical data suggests an SVR rate for treatment naive patients at around 70% for GT-1 patients, and a possible duration of 24 weeks for some of the patient population. This may change slightly as the drugs approach market, but this would be the plan I’d opt for in your position if possible.

Best to you—

Bill

[banarep]

right now, i would say you are a slow responder, but the rise in viral load from week 8 on is not the greatest of signs.  However, that being said, the only real number that matters at this time is week 24.  I think you stay with it and see what happens.

[Rockerforlife]

Looks like you got tuff virus on your hands,i think 1b is the hardest to treat.This is just my opinion, if it were me,I would  ask to start the intergen now because it looks like by your VL numbers you are not going to go UD by week 24 regardless if you continue this way.Other option is to go on the PI drugs coming out in a few months if you can afford to wait...you are a non responer on my view....you need the protese drugs

[sunshines76]

Thank you, Bill. I have an appointment with my doctor next week, will ask him what his logic is... Does it sound to you like infergen is not going to be helpful either if I get switched on it now?

[Rockerforlife]

There will be new trials with the new PI drugs soon and they are even more effective than the current ones.One is the BOCEPREVIR 00518...10 x more effective than than the BOC trial i am in now,dont give up,there is good reason to bo optimistic....what stage are you....2...3..?

[sunshines76]

I agree - it looks like I am a slow responder, or to be accurate what they call "a partial responder", which at the end almost always lead to relapse... If I found at least 1 person on this forum who had the same stuff going on and achieved SVR, I would be delighted to get my hopes up... :)

[Rockerforlife]

In my first round of TX my VL was 25 million,i was at 475 VL at week 12, somewhere between week 12 and 24 i went UD,after 48 weeks of TX and relapsed.I was geno 1a.

[sunshines76]

Thank you for your encouragement! I am debating between asking to switch me on infergen now or waiting till PI will be available. Can't find any trials on Boceprevir going on in Seattle/Tacoma area though... Actually, can't find any trials that would be suitable for me in this area now.

I refused to do liver biopsy, so have no idea what my stage is. But my liver enzymes have always been normal, never experienced any symptoms either, except I have always run 37.2 fever. Got diagnosed with HCV by occasion - when did all my labs before going through IVF treatment. Then picked up my childhood medical records (I was born in another country), and there was a note in my birth chart/hospital release - nonA/nonB hepatitis... I guess, that was it - as I got blood transfusion when I was born as a preemie.

One thing for sure - I will not give up :) !

[Bill1954]

Infergen *might* change the viral kinetics enough to elicit a response; as well as a change from Pegasys to PEG-Intron. I was a late responder in my initial treatment attempt; I didn’t achieve a 2 log reduction at week 12, but missed it by several hundred IU/mL only. Trying so influence statistics, I increased ribavirin intake from 1200 to 1800 mg/day, and increased duration from 48 to 56 weeks, but relapsed within 30 days post treatment.

On second treatment, I was prepared for Infergen, but my hepatologist didn’t have much faith in the numbers it provided. He suggested switching from Pegasys to PEG-Intron; I increased the ribavirin again to 2000mg/day, and increased Tx duration to 96 weeks. This produced SVR (sustained Viral Response) finally, but it was a long road.

If I had less fibrosis, and was in a different time frame, I might have deferred treatment to a later date. At that time, the protease inhibitors were still more theory than they are now. With the final data in from phase three trials, there release now appears imminent. I had late stage 3 damage, and had possibly progressed into early cirrhosis by the time it was all said and done; this amount of scaring can change treatment dynamics, obviously.

Again, talk with your GI or Hepatologist, and get their take on the situation again. You might ask for an additional opinion as well; null response does put you into a hard-to-treat category now.

All the best to you, and check back on this thread early next week to get other views on this… the forum is generally quiet on weekends.

Take care—

Bill

[sunshines76]

Wow, I can imagine how it felt to see your test results showing you relapsed after the tx was done. How are you doing now? Are you participating in any trial now?

[Bill1954]

Unfortunately, it’s possible to progress into and through significant damage, and even cirrhosis with normalized liver enzymes; these just aren’t an accurate way to predict damage. About 30% of HCV patients present with in-range AST/ALT.

If you cannot undergo needle biopsy, even one of the so called ‘surrogate’ blood tests such as Fibrosure/Fibrospect might give you an idea of your grade and stage of disease. I haven’t heard much positive feedback on these tests; but they may be better than a guess.

Are you seeing someone at University of Washington now?

Again, nothing but the best—

Bill

[sunshines76]

Really, I am ok with a long road, will do anything to get rid of this annoying HCV... Your story is very encouraging, Bill! Did you have 1b genotype?

[Bill1954]

No, I was GT-1a, but I believe there is very little distinction between the two, at least from a clinical standpoint. I also have insulin dependant diabetes, which in itself is considered a negative predictor for SVR. I do consider myself very fortunate :o).

Bill

[sunshines76]

No, I am not seeing anyone at UW. Would you advise a specialist?

[copyman]

I agree with some of the others that waiting for the new drugs would be the best bet.

Waiting to see at 24 weeks is just prolonging taking very harsh drugs, most likely for nothing. The "2 log drop by 12 weeks" and  "must be undetectable by 24 weeks"  protocols are soon to be a thing of the past. To have a real chance to clear this virus you have to be clear by 12 weeks at the latest! The up to date Hepatologists are starting to use this protocol knowing not many SVR responding later then 12 weeks. They are realizing that clearing late gives the patient very little chance to SVR.

Sounds like you may have been UNDER dosed with ribavirin. What is your weight and how much riba are you on? Did your HGB drop a few points?  By you saying you feel good is not a good sign when on TX. When this TX is working properly most will feel bad. Usually from anemia cause by the ribavirin.

Best of luck what ever you decide

[sunshines76]

I am 180 lb, taking 1200 mg ribavirin a day. Never became anemic, ALL tests come out normal, except for viral load...

[Bill1954]

No, I’m sorry; I don’t know any staff personally. I have heard from others here that they have an excellent hepatology department though. Any time you can connect with a large teaching hospital, they are more likely to provide cutting edge knowledge and service to patients than a regional GI doc.

Bill

[newleaf09]

Bill is a trustworthy source of information.  He cured some time ago but never lost his fascination for the disease and keeps abreast of what's going.  He is also the only poster I consistently agree with and I would stand  behind his opinion on your situation as well.

Having only a temporary dip in your VL shows that the interferon helped a bit at first and then failed to establish a pattern the way it should have. I don't think you are a responder.  Hep C is a relatively weak RNA virus that is just very good at hiding from your immune sytem.  Interferon can induce extra virus killing cells but they can't do their job if they can't 'find' the virus.  Other forms of interferon exist but it's hard to predict if they will be more effective against your strain than the current form you are on.

1b's are not more resistant than other geno's; that was a finding in one small study; wish they would stop publishing those little studies, since they are so misleading to net searchers.  I was a 1b with a low VL and cleared after 1 week because I was one who was very responsive to interferon.  Many, many people who ARE responsive have dramatic, miserable drops in hemoglobin.  You don't have that SX.

The current research goals on HCV Treatment are to shorten TX time in order to reduce the patients exposure to interferon, which can cause permanent damage to the human body from long exposure.  If it were me, I would try to damp down that desire to "do anything" to keep treating, get out of TX and wait for the triple therapy (Interferon/ribavirin/protease inhibitor) to be approved in 2011.  The current PI's being trialed for 2011 release are showing good promise for both non-responders and relapsers.      

[Marte313]

I am also going for the "wait for the new drugs", since trials has showed that peg alfa-2a (pegasys) gives best results for your GT of the current treatments.

[copyman]

you are a perfect example why PCR's should be givin early & often in treatment so doctor can adjust RX. Perhaps your Riba could have been increased to 1400 or 1600 until UNde and noticeable drop in HGB. Then decrease back to 1200. Even adding something like Aliana is worth a try early on. Whatever is takes to be undetectable by 12 weeks !

[Rockerforlife]

Yes,i am currently in a trial,check out my profile for details,and Bill,WOW...didnt realize you did such a long TX,Were your sdes really bad?...How are your EOT sides?


A total commitment is paramount to reaching the ultimate in
performance." -- Tim Flores

[sunshines76]

Do you think it's too late now to increase my ribavirin dosage? If it's done after 12 weeks?

[sunshines76]

I am thinking about waiting till 2011 - I just hope that in 2011 we do get the drugs instead of being told to wait another 5 to 10 years... The fact that I probably had this virus in my body for the last 30 years kind of scares me, although on another side, I really feel great and am very active, full of energy. My pressure is my kids now - I know I have to get rid of this virus to stay a healthy and happy mom for them.

[HCA]

Ribavirin has no role in initially suppressing viral load.
It (helps) prevent relapse by causing mutational error when the virus rallies against the effect of the interferon.It is most important during the period when the viral load is being driven down to undetectable levels.
It's all rather involved,but if it gives you any comfort your non-response is down to your lack of sensitivity to interferon.
It is true however that if you did not experience a significant drop in haemoglobin you could probably tolerate more ribavirin next time..

[Bill1954]

I believe the difference in waiting for the protease inhibitors this time, as opposed to previously is that most of the data is in from phase 3 study now. The efficacy and tolerability studies are now complete, and it appears that eventual release is now imminent. If one is to believe press releases, Telaprevir should be available in 2011 sometime. Now whether this translates into adoption for Standard of Care by insurance companies is an entirely different story. I believe Vertex plans on submitting the NDA for TVR in early 2010; we’ll know more at that time.

Hang in there--

Bill

[Rockerforlife]

Ill let you know in 5 days if the boceprevir phase 3 RESPOND 2 trial worked for me,i get my PCR resuts Friday.

[sunshines76]

Very best of luck with your PCR results! We'll be waiting for good news!

[copyman]

No, I do not think increasing Riba at this time will help.

I disagree with the other poster that  Riba is not important early on. There are studies that show it to be almost as important as interferon, i.e. studies that did not have Ribavirin and the interferon did not have much effect at all by itself. On the other hand pre-dosing ribavirin showed great promise and the new PI drugs even need Riba "early on" to work. So it is obvious that Ribavirin plays a MAJOR role in any TX combo right from the beginning. Granted it does take some time to build up in someones system but it starts working immediately.

[sunshines76]

Increasing riba now will not work because of a chance that virus has mutated or developed resistance by now? Is that why?

[sunshines76]

Bill, I will definitely hang in there :) This week is going to be important in assessing my current situation and deciding what's next, can't wait to see my doc now. Will probably seek a second opinion too. But thank you so much for all your comments - and everyone's comments here - and sharing your story. You probably are fortunate, but you are definitely fortunate because you fought the beast fearlessly :) I am now much better prepared for my next appointment, have some good questions to ask.

[HCA]

You have completly misunderstood me-I did not say ribavirin is not important early on.
Qiute the opposite in fact.
I have been advocating the pre-dosing of ribavirin for years as my old posts reveal.
I simply said that it does not eliminate the wild type virus,but rather it prevents the design of a successful variant.

[copyman]

Yes, I did misunderstand. I should have known that you of all people would know the importance of Riba.
Take care

[sunshines76]

Sorry, I probably ask dumb questions - but did I understand both your and copyman's posts as suggestions that in my case the virus has probably successfully mutated and now pegasys will not work for me anymore?

[HCA]

It means that the pegasys can't knock the virus down during this particular round of treatment-like you say the virus has got the upper hand.
That's not the end of the story though-when you treat again the response could be very different,particularly if one of the new drugs is added to mix.
Hep C treatment is racing ahead and you will get to benefit.

[nygirl7]

Hang in there sunshine...if you look around in here you will see many people that had to retreat and were successful at last.

One of the things that might have been rather telling for you earlier on is that you experienced relatively no sides.  While it's not scientific to the nth degree...oftentimes this can mean you were underdosed to begin with.  Sad fact with this treatment is that some major discomfort is not a bad thing.

As you have read now early PCRs are crucial.  Myself I was a geno1A and also 1B.  There is no real difference between the two but I was paranoid it would be double as hard to get cured so I over did the riba in a major way.  Still at week 12 I was detectible and it was only at my 24 week test I was UND.  Like Bill I extended (but only to 72 weeks.....he did 96 which still amazes  me).

The point I'm trying to make here is that a lot of us really see tailoring your treatment as really crucial.  That is why early and frequent PCRs are so important...if you aren't hitting the right marks or something you can always try to tweak it up a bit.

Your best bet is to stop and regroup and then attack it again full tilt.  l read the thread but don't see your stage liver damage (I'm at work and always have to rush so I could have missed it easily).  If you have the time waiting another year or two after this long isn't a big deal and the PIs show so much promise.

If you do have later stage then finding a doc who might be a bit more aggressive and up to date on things would definitely be the way to go. You just gotta work on getting to UND by week 12 or if not by week 24.  Completely.

Good luck!

[sunshines76]

Thank you so much for the encouragement! I know it might take several tries and a long time, but at the end the dragon will be beaten :) I am so glad I found this forum, it's really helpful to see all the stories and what other people have to go through and what they can advise from their own experience. And all the encouragement here definitely helps, a lot.
I talked to my GI doc today, he is suggesting to wait till 24 weeks on the same treatment and then decide whether switch on infergen or wait for PI drugs to enter the market finally. But we are also seeking a second opinion now, with a hepatologist, will know more by the end of the week.
In general, though, life is good. Seriously :)

[sunshines76]

A quick update. At week 16 pegasys + riba my viral load was 94,000 - killed the last hope - obviously I was not responding to this therapy. Last week switched to daily infergen plus riba. First two days on infergen were TOTAL HELL - very high fever, chills, and pain allover my body. Couldn't sleep at night at all due to the pain. But after two days - I am back to feeling normal again. The only problem - my hair loss got much worse. In three weeks will have my viral load labs done... Keeping my fingers crossed.

[copyman]

not sure if you posted this but do you know what, if any liver damage you have? if you don't have any or little why not wait for the new drugs? why put yourself through this when new drugs are right around the corner. The only reason I would think a doctor would put you on infergen is because you have severe liver damage.  Other then that you should NOT be on it. Just my opinion of course.

[sunshines76]

I refused to go through liver biopsy, so basically don't know how damaged my liver is. What happened was we actually scheduled liver biopsy and then the day before the procedure I started panicing, got really scared to go through it. Which is really funny, because I am usually pretty calm and don't feel scared about medical procedures. Went through 3 major surgeries in my life... But this time I was really scared. And my doctor said there was no need to go through it if I was so scared.
As for infergen - I am doing ok now. Became slightly anemic, have fever, but nothing like what I experienced during the first two days on this drug. Once again - I am feeling ok, so will try to go to at least week 12 on it and then decide based on the results. My doctors said that they will get the new drugs in 2010 for trials, so if infergen doesn't work for me either, then 2010 it is :)

[bee1236]

by beatriceBee

just diag w/ hep c 1a all normal blood test, sched. for liver biop. hear u dont have to take one, will u still b eligible for treatment?

[copyman]

sunshines76:

Glad you are feeling better.
Sorry to beat a dead horse but I just don't see any benefit in subjecting yourself to infergen for 12 weeks after not responding to SOC treatment. Did the doctor what the benefit was and what is his plan if you do clear after 12 weeks? Since you didn't have a liver biopsy the only way would be is if your labs showed signs of severe liver damage. Maybe someone else could chime in but I don't even think this is standard protocol without severe damage?
The new drugs will be out in 2011.
PS, Once again this shows why a liver biopsy is so important in helping to make treatment decisions. If you knew you didn't have any or minimal liver damage you could feel confortable stopping and waiting for new drugs.

bee1236:
Yes you can still treat without a biopsy but it can really help in your treatment decision. A perfect example is what you see in sunshines case above.
The liver biopsy is painless and over in less then 5 mins. I only had some shoulder pain for a few hours after. good luck

[jacksonblue]

Hello sunshine i must agree with copyman if possible i think you would be better to wait for better treatments . I became so determined with getting rid of this viris treated 4 times in 10 years it consumed my life at times i think i treated to agressively and wish i had stepped back and thougt things out .The last treatment seams to have worked in 24 weeks only with tvr .BEST OF LUCK with what ever decission you make regards steve

[jacksonblue]

I was also 1b

[sunshines76]

Once again, even being on infergen now, daily shots, I feel pretty well, better than before tx. It was only the first 2 days that were really tuff. It's unbelievable, but I have MORE energy now, while on treatment. Before treatment I used to feel so sleepy all the time. And now I am full of energy - I have enough energy to spend very active days with my 2-year old twins, while my husband is deployed to Iraq, and I don't get much help from anyone.
I know it sounds incredible - I've read so many responses stating how hard tx is for some. Not for me. I guess, this is the main reason while I agreed to try infergen.
Another reason being - I have a great health insurance that covers all expenses, so I'd rather try to get rid of HCV while I have this insurance - who knows how long we will be able to keep it.
If infergen helps 15% of non-responders, who knows - perhaps I will make it to those 15%. If I am lucky, that would mean that by the time my kids turn 3, and my husband is back from Iraq again, I won't have to think of going through another tx, but rather can have tons of fun with my family.

[sunshines76]

It sounds so awesome when you can write "I WAS also 1b". Congratulations!

[ditzybabe]

"The current research goals on HCV Treatment are to shorten TX time in order to reduce the patients exposure to interferon, which can cause permanent damage to the human body from long exposure. "

How does that happen? I've had one form or another of interferon for over three years.

[newleaf09]

You mean how does damage happen from long term exposure?  Search this forum for starters to see what the damages can be.  I stopped reading those because I thought that some of the problems were age-related and people were still pinning the problems on IFN, but it's obvious that that's only the case for a few people.  Others have real damage.  You already know that some people are much more responsive to IFN than others and I think the damage can be just as variable.  The interferon is part of the body's natural immune response and when we add extra with the shots, it ramps our own immune system up even more.  I suspect that it causes autoimmune responses; makes us allergic to ourselves and causes the body to attack itself.  Can cause nerve damage, lung damage, permanent thyroid damage, arthritis.  Ideally you would be on IFN for the shortest possible time, to be sure no systems got damaged by the drug.  It's a miracle drug, but I wish we could defeat the virus without IFN at all.  Research may never arrive at that point.

[sunshines76]

I did my bloodwork on monday, including PCR, this week. On wednesday the lab called me and wanted to redraw my blood. Said they have contacted my doctor already and I just needed to come in for additional testing on PCR only. Noone could give me an explanation why I had to retest. I am looking forward to getting the results next week. It's been almost 5 weeks on daily infergen now. I am feeling ok (if forget about anemia), hoping for good results.

[sunshines76]

I had my doctor appointment - to review my week 4 PCR. I am pretty happy today - I am still detectable, but the result showed <43 (down from 94,000 before starting infergen). My nurse said it looked like I was right on the border and that at 8 weeks we should expect to be UND.
:)

[annieCinMD]

Great news! Keep us posted when you get your 8 week UND!

[Magnum]

Funny, but that’s exactly what my doctor did with me. However........

I would ask your doctor some very specific questions about Infergen. It is a powerful drug that nearly did me in. Not trying to scare you, but my Gastroenterologist will not use it on any of his patients anymore. This is what he personally told me two weeks ago.

Apparently he has had other patients who had problems with it. I’m no doctor, just a non-responder, but I’m passing on to you what my doctor said to me. What you do with it is up to you, but again, I would question your doctor about the past history of having had patients who may have developed problems with it. Otherwise, the best of luck, and also ask him if you can wait for the protease inhibitors to be released in a year or so...

Magnum

[sunshines76]

Does anyone know what is the most sensitive PCR available? I always thought that if you were less than 50, then you would be UND. The test that I was doing, apparently detects HCV at 43 and above. Are there even more sensitive tests now?

[sunshines76]

Magnum, could you, please, be more specific - exactly what your doctor did with you? I suggest from what you wrote that you had to stop infergen? What exactly happened? My other tests show that I've developed mild anemia, so they are monitoring my CBC every week. As for actually feeling any side effects - so far I can't say I feel anything major: hair shedding, light fatigue, that's it, I can deal with it. I wonder if more side effects to come...

[Magnum]

I’m 1a. Instead of the 15mcg (typical daily Infergen dose), the doctor had me on 24mcg because I did not respond to three prior treatments and this time he was determined to clear me. On the fourth month, this caused my ALT and AST numbers to go into the 800's. My urine was chocolate colored, I was jaundiced and headed for total liver failure.

If your doctor gives you the normal dose, you may be fine. My doctor will not give patients even the normal dose anymore. Just passing on what he told me. I would ask your doctor... Best of luck in clearing.

Magnum

[sunshines76]

Thank you for sharing your story, Magnum. I am sorry you had to go through that. I am on 15 mcg daily, my ALT/AST are within the norm. I drink tons of water and side effects are bearable. I hope I get through the whole 48 weeks successfully. Today got my 8 weeks PCR tests taken. By the end of the week will know if I have a good present for my birthday :)

[sunshines76]

My doc just called - wanted to give me the good news - my 8 weeks PCRs came back UNDETECTABLE! I understand it's only the first step to success and it doesn't mean yet that the virus is gone for sure, but... I am having a wonderful day today. One more thing to be thankful for :)