Relapse

Well, it appears as though the virus has returned for an encore presentation. 30-day post Tx PCR shows a viral load of 112,000 IU/ML. These results are from a lab drawn 30 days after completion of ribavirin, 37 days after the final IFN injection.
The assay used was Quest # 354645X, real time PCR HCV RNA quant <50 IU/ML. My treating doctor is currently in Europe, and my next scheduled appt is May 1st.

Stats:
Male Caucasian
51 years old
HCV genotype 1a
Prior Tx baseline VL was 75,600 IU/ML
Biopsy on 1/22/05 indicated inflammation grade 2, fibrosis stage 3/4
6

[jmjm530]

Our two last posts crossed.

It seems like you did have contingency plans and daily infergen is definitely one way to go.

As I mentioned before, my current contingency plan as a stage 3 is to wait and then  hopefully re-treat with newer drugs. This was the recommendation of two hepatologists I respect.

I understand your reluctance about another biopsy but you might consider getting a Fibroscan with Schiff in Miami or Afdhal in Boston: http://tinyurl.com/nbavn As you probably know, Fibroscan is different from the Fibrosure blood test -- sort of like a special ultrasound that measures liver stiffness and then correlates it with liver stage.

You may or may not qualify for their Fibroscan trial but I believe either would see you as a private patient. Fibroscan or not, you couldn't get a better second opinion than from either of the two.

All the best.

-- Jim

[fishdoc]

Hey Bill.  I am so sorry.  I am two years younger, but I am overweight, which as you know is a strike on the bad side, and 1A, VL 2.9 mill pretreatment (bad again)... so my expectations are also minimal, given that I am usually just not too lucky.  If I miss the coin flip, I think my plan might be supportive dose of interferon, until some of the new  meds come on line.  Any chance of trials in your area??

[Mister beagle bailey]

Bill, I am so sorry and can't find the right words because any thing I say will not change the out come.  But like Jim said the new drug is just around the corner and shows much promise.  Just saw a few weeks ago on the news that the drug Vertex should be on the market by the end of the year or early 2007.  It's showing so much promise that it's almost ready for release.

Beagle

[Bill1954]

To answer your question regarding assay sensitivity, my doctor used the local hospital default test; bDNA quant <615 IU/ML to establish baseline and 12 week values. As my knowledge base expanded, I requested a more sensitive test. My doctor feels that the more sensitive TMA assays have research value, but little clinical value. We compromised by using PCR <50 for the remaining labs.

My ALT/AST baseline numbers were 275/109, and EOT 93/58. No LFT

[Bill1954]

Fishdoc says"....given that I am usually just not too lucky...)
LOL! We *must* be kin!

[mikesimon]

I want to say how sorry I am about your results. I relapsed once and I didn't handle it nearly as gracefully as you are. I hope that your liver has improved with the treatment and I think it's reasonable to belive that the TX has at least halted further deterioration if it didn't improve the achitecture. I wish you the best. Mike

[Rogirl]

I am so sorry to hear of your relapse.  You are so eloquent and kind to point out in spite of your news, that good things do happen.  What a great person you are to encourage others--a sign of a "true human" person to look beyond their own misfortune (which we all hope is temporary)and provide hope for the future.
From one who hasn't begun tx yet it helps to hear the stories of everyone regardless of the outcome.  I am inspired by your story and wish the very best for you.

[Bill1954]

(continued)
(In my individual case, anyway).

Looking forward, I plan to request an additional PCR for confirmation, then the next step will most likely be a Tx of daily Infergen/riba. This was our contingency plan as of my last appt.

Keeping in mind that there is more than one endpoint to treatment, hopefully I will have seen some histological improvement. At this point, however, I don

[jmjm530]

It's hard to formulate the right words when someone who has fought and endured as much as you have goes into relapse. I am so very sorry.

As to treatment length not being enough, 36 weeks additional was a reasonable decision weighing risks against rewards. Nothing definitive to suggest that adding more time would have changed the outcome. I'll speculate that your main negative predictor was your slow viral response.

Two questions -- how sensitivity were the viral load tests you took during treatment? If you remember, Goofy posted a study that suggested that 50 IU/ml may not be sensitive enough and some folks passing that test may still harbor the virus. And secondly, do you know what your enzymes post treatment and at relapse?

I'm sure you haven't had time to look ahead, but the newer protease inhibitors now in trial like Vertex might be something to look at. My understanding after talking with a few in the know is that they potentially will be of great benefit to people like yourself who responded slowly to the current drugs. Given the current drugs and current doses, just don't see 72 weeks or 2 years of combo treatment as a first choice. Should I end up in your shoes when my next PCR comes in, it certainly would not be my first choice.

Again, so very sorry, but you're a fighter and will win.

-- Jim

[goldyn]

Im so  so sorry hear about your relapse,but you seem to have a good outlook on eveything, and your right at least you gave your liver a much needed chance to heal , and thats always a real good thing.

               God Bless you on what ever decision you make.

                       angie

[mikesimon]

I question the projection for Vertex-950 being available late 06 or early 07. The information I've seen suggests 09 at the earliest but things do change quickly - but usually not FDA drug approvals. Mike

[slowsouthernstyle]

I am sorry to hear about your relapse. I relapsed 3 times and said no more meds for me. I am not sure about the weight issue being the factor in relapse. I am at an ideal weight and have always been on the thin side so for me it was not the problem. I think genotype 1's are in a less than 50% category for response even  under the best of conditions. The new drugs will be a welcome sight for many. I sure hope they work.

slow

[Califia]

No technical response here--although you have received some solid feedback above, I believe--just my full out sympathy and fellow creature yelps of anguish and aw, sh*t, man, not fair, not fair.  Yes, your linguistic calm and control and grace under fire are indeed impressive, but then again you're a rare and admirable human being and I hope you continue to fight like hell for your survival.  Mother earth needs you.  And if  you should need anything, you just call (so to speak),  y'hear me?

[Bill1954]

MBB-Thank you for the heads up regarding Vertex 950, etc. I

[fishdoc]

yeah, I don't buy lottery tickets, and if i do, i never check them!!!

[OnAPrettyPoison]

I am so sorry.  My heart goes out to you - this really sucks when you fight so hard, hope it is over, and find out you have to fight again.  You did fight valiantly and have accepted the relapse with grace and honor and with the determination to fight it again.

My docs had told me if I didn't initially respond fast with the Pegasys that they would switch me at 12 weeks to the pegintron.  They did consider it a stronger drug, mainly based on the fact that (1) patients may respond better to pegintron when didn;t with the pegasys, and (2) the side effects did seem stronger and more unpredictibible as to timing.  Have you considered trying the other peg before going on infergen?  My docs seemed to have no problem with switching interferons mid stream if the first did not respond to their satisfaction.  Just curious. did you have severe anemia while treating?  Best of luck and keep us posted.

[Bill1954]

Ina--I understand the notion of a break between treatment to let our hemo components normalize, but my blood held together quite well throughout Tx; white cells dropped a little but the segs remained high giving me a respectable ANC value. Hemoglobin remained above 13.4; no epo necessary and riba at 1800mg/day? I

[OnAPrettyPoison]

Almost wonder if it was a riba absorption issue?  I know some studies were discussed that anemia was a positive predictor.  Have you thought of maintenance dose of interferon until better drugs?

[jmjm530]

I agree with DD that Peg Intron might work better than Pegasys. But there's still the issue of riba absorption whether you treat with Infergen, Pegasys or Peg Intron. One strategy -- and this is my own home-cooked approach based on no medical background -- is keep incrementally increasing riba until you force your hgb down to the lowest safe level you can tolerate AND concurrently take 40,000 units of Procrit per week. In theory this should give you the highest serum riba level your body can tolerate. Of course the downside is more side effects and if you miscalculate it could end in transfusion of temporaty termination of treatment.

DD,

Check out ASmile's post in "Pre-tx Consultation" thread above this. In a nutshell, she's re-treating for the second time on Infergen and has a slow week 4 response. Wants to know her odds for success. I know the week 4 response is important with peg and riba but not sure with Infergen.

-- Jim

[cuteus]

Bill, this is one thread title I did not want to see! darn!
I think you are correct in assessing that 36 wks past undetect was not enough in your case, and if you recall, the Drusano study from where this number is derived was theoretical and stated that confirmation was needed.
The actual studies out there paired 48 wks vs 72, with 72 having the best response for slow responders. My feeling is that going the longest your body can tolerate, with matching tx length to actual studies is the best way to go. Mikesimon and I both did 72 and so did dollface and others. It worked for us. In my case I went the 72 wks route because of my detectable status at wk 12. I believe that the two log drop "benefit" goes out the window when you are still detectable at wk 12. So far I read one study where the positive PCR at wk 12 is the key to consider extension. They and other studies do not mention the 36 wk post negative PCR. You could say that they seem to randomly select 72 wks as opposed to 36 beyond a negative, but if that is what they found to work the best in actual studies, that is what I would follow.  What ever risks there might be going beyond 48 wks, do not seem to be a higher percentage in adverse events reports. I believe there was a 3% difference bt 48 wks and 72 in the study I read.  I wish people would stop quoting the 36 wk as the gospel for extension, especially for slow responders.
Many re treaters do achieve SVR by doing tx with the same meds longer or the opposing med, ie if Pegasys was used, the next time is Pegintron and viceversa. Not all go the infergen route to achieve SVR.
I think you have a good shot, because you did respond to the meds, and if there is any validity to the virus becoming resistant upon recouping, you might not want to wait too long for a stronger mutation.
In the case of slow responders, if they are tolerating tx fairly well, they should do at least 18 months or at least a yr from clearance, maybe more. Again, if tx is tolerated well. THe so called risks with longer tx are statistically insignificant  in at least one study I read ( I have the link at work). If someone is going to have an adverse event, it will happen within the first 6 months of tx, so it can happen to anyone, even the genotype 2.
best luck in your decission

[Mister beagle bailey]

About the vertex, I live in Fl. and they had it on the evening news.  Don't know much else about it but when they said hepC it caught my ear so I listened and that's what someone from the company said.  Who knows if it's true or not, maybe they want their stock to go up.  But if that's the case their taking a gamble putting it on the news, I would think.

Beagle

[dyce]

I'm sorry for you there bill. Was hopin when I read you finished the post tx pcr would stay undetectable. You seem very even kiltered . I'm sure you'll beat this , your to strong willed and approach the battle with good logic, to lose.

[DoubleDose]

The major part of you problem revolves around the late initial clearance, at week 20.  Any genotype-1 who clears later than 12 weeks is in for a tough course, but can achieve SVR as long as they do get that initial clearance by around week 26, at the latest.  I think that for late responder, type 1's, most of the HCV doctors seem to be moving toward the 72 week course of tx.

Now I did 14 months on my first tx, started with 3x/week intron, then went to daily intron, still could not get undetected, and at about month 8 I went to high dose daily infergen.  I got undetected quickly, and was able to go for another five months, ending undetected.  I relapsed in a month.

My second round was with high dose Peg-Intron, and full dose riba, and I got undetected at week 19.  Late again, but more in the ballpark for potential SVR.  I went a total of 72 weeks, using lots of Procrit, to keep the riba up, and finished undetected.  I have been SVR now for two and a half years.

Duration makes a big difference for GT 1 late responders, and I believe that these patients need to stay on tx for at LEAST a full year after the undetected date, if not even longer.

Sorry for your relapse, but given your ability to get undetected, you most probably can get the SVR with the right dosing, AND the right duration.  You may want to consider Peg-Intron on your next round.  I truly believe (as does my doctor) that it is better in tough type-1 cases than Pegasys.  It also has more side effects for most people, but is very doable.  I think it is easier and more practical than daily infergen.

Best Wishes!!!!!

DoubleDose

[Bill1954]

OPP
I appreciate your thoughts and comments. Regarding the switch to Peg-intron, I would be more concerned with the duration of another Tx with any PEG-IFN (minimum of what, 72 weeks?) than the thought of Infergen treatment. I

[NYgirl]

Someone just brought up to me the fact that as far as anybody knows...where DID this magic 36 weeks after come from?

Is there ANY hard core studIES that prove this out?  You know me...I am all for the MORE the MERRIER but I am wondering as strong as these drugs ARE and the fact that I already have gotten ONE AUTOIMMUNE disease as a result of them - is this really a supported FACT or a number we bandy about?

As someone who didn't clear until about week 20 as well AND a 1A and 1B ... I always thought to go at least 60 or 72 but I will need backup to convince my DOCTOR of this. And the insurance company as well.

It doesn't appear that doctors are really aware of this 36 week fact.

[jmjm530]

Bill: Hemoglobin remained above 13.4; no epo necessary and riba at 1800mg/day?
-------------------------
I wasn't going to bring up the riba issue right on top of your relapse but since you seem to be asking the question here...

Sweedish studies suggest that riba absorption is directly related to level of anemia. In your case, one could speculate that your serum riba levels were not at a therapeutic level regardless of the fact you took 1800mg/day. Some,  I believe, in the Sweedish study took double that amount. In my case, my hgb ended up in the 11's but on 60,000 units/Procrit a week. This is not to say you should try a high-dose riba approach like in Sweeden. Their group was small, sides effects high, and we don't have the proper blood tests in this country to properly monitor serum riba. But I do offer it as a possible reason for relapse.

Regarding what some other have said...My understanding is that longer treatments are associated with more side effects, i.e more risk, and often higher drop out rates. I believe some of the shorter course studies have documented this.

As to the risk of more resistant virus/mutation while resting between treatments -- my hepatoloigst as well as others feel that folks will do better the second time with the 6 month or so rest between treatments as the immune system has time to recover and get stronger.

There is also speculation -- no studies I'm aware of -- that treatment and re-treatment has an accumulative effect, with one tx training the immune system for the second time. This also seems to argue the fact that resistant viral mutations take place between treatments.

As to your own personal decision, there is no right and wrong here, and no real study data to prove things one way or another. I thought I'd just balance out the discussion for others who may decide to approach it differently.

-- Jim

[jmjm530]

NY says:Someone just brought up to me the fact that as far as anybody knows...where DID this magic 36 weeks after come from?
--------------------------------------------------------------
Unfortunatly, there's no magic in hep c treatment.

The 36 weeks came from a researcher named Drusano, and it's not a "rule" as some state but a model that Drusano himself needs further exploration. Still, it's commonly used by many hepatologists -- good hepatologists -- to extend treatment with some slow responders.

My doctor, for example, uses variations of the model and extended my treatment 48 weeks beyond non-detectible for a total of 54 weeks.  He cited my age and histology as the reason to go beyond the 36 weeks. If he treated Bill, he probably would have also suggested 48 weeks beyond non-detectible. I should add here for balance that three other hepatologists I consulted only recommended I extend 36 weeks beyond week 12 -- which if you read he Drusano study very carefully is the minium point you should start adding in a conservative strategy, since the study didn't test before week 12.

We have an educated lot here and all the options are being put on the table -- Extend with current drugs, extend with another peg, daily infergen, wait for trials, the problem is the riba, treat right away, wait six months, etc, etc.

I believe any hepatologist honest with himself will tell you that at this point we really don't know enough to say what is the best approach for a relapser. So, in my opinion an awful lot depends on what the patient him/herself is up for. Bill is one of the smartest guys here and I have a feeling he's going to do exactly what's best for him. Even though I'd like him to wait for newer drugs :)

-- Jim

[tina-b]

I'm really sorry to hear that. Some days suck! When my husband relapsed again, his doc suggested a "Medication Vacation".

I think it was the best advise he ever got. (that isn't saying it is for everyone)

Good Luck to you!

[Magnum]

I'm sorry for your relapse Bill. Ask your doctor if you can wait for the VX-950 Protease Inhibitor. I've been told it should be out 2007 or 2008. Best of luck to you. We will all be victorious.

Magnum

[Forseegood]

wow, everything wise has already been said, just so sorry to hear this, but I really thing youre one of the voices of reason and rationality around here, and that should bode you well as you decide what to do next...I know at any rate you'll sure be glad to get off the dang meds! for awhile at least...blessings as you continue your journey...

[SJL]

Sorry just doesn't cut it, does it? As a 1B, stage 3, grade 4, and having responded & relapsed twice on therapy, Peg-Intron/Riba & Infergen daily, I have elected to go on Pegasys Maintainence, and I am not sure if I will attempt to treat again.
The Pegasys seems to be holding the virus down & I know that it is unlikely that I could attain SVR on it.

I am not sure of any side effects which you encountered, but I was one miserable person on both therapies and have been diagnosed with Neuropathy, a direct result of treatment. I had been told that sometimes the interferons can cause permanent sides, so I can't say I didn't know. My feet & legs go numb up to my knees, resulting in 8 falls. For me treatment is not the answer presently.

My Hepatologist has stated that I have at least 10 good years before virus might possibly cause problems. I am presently 62 & female. I have fought the battle for over 3 yrs. now & I want some kind of normalcy in my life, which has prompted me to stop therapies.

I know we all carry this disease differently, some easier than others and I am so thankful for that. I guess I am telling you my story to give you another view to contemplate. I know that the interferons did help some & I thank God every day for this.

I was a gung-ho, let's treat like their is no tomorrow, but the neuropathy has certainly changed my mind. At this point we are not sure if it is reversible or not & I am having epidurals, attempting to help.

This in no way means that you should not re-treat. I only mean it to be vital info for all who are on treatment. Just watch yourself closely as sometimes the meds are worse than the disease.

Bill, with your positive attitude I am sure that you will reach SVR. If I can be of any help regarding Infergen answers, I am here. Be Well & the decision you make will be the right one!

Sandy

[Bill1954]

My goodness,

Everyone in this forum should take a silent moment to give themselves a hand. The responses I

[beamishboy]

sh!t,Sh!t,sh!t......!!!!! sorry to hear/read  about the return of vl..dang bill..does this mean yur not gonna build my semi-circular stairs??hang tuff big fella and GOODLUCK on whatever path yu chose

[strator]

Bill I've nothing but good wishes for your health SVR. I'm sure with the mental preparedness and emotional acceptance you show, that you will handle whatever you decide and face.
Thank you for posting with the grace you've show in a difficult time.
Be Well,
Don

[GoofyDad]

Bill this is a huge dissapointment for me personally. You've been exceptionally helpful and supportive to so many here, making it particularly hard to watch this misfortune land on your doorstep. I wish you the best as you make your decisions and turn the page into the next chapter. Your attitude is enviable. Keep it up, sir.

[GoofyDad]

You said: <i> ....if there is any validity to the virus becoming resistant upon recouping, you might not want to wait too long for a stronger mutation.</i>

Where does this come from? I've seen facts that seem to  contradict this position, but nothing supporting it.  

[Califia]

I just want to make sure that this telling piece of data doesn't get lost in the larger discussion.    Frankly, it has me reeling.  

Bill informs us that "when I researched the possibility of testing for plasma ribavirin concentration, I found that the test isn