UND again at Wk 26 - What Chances of successful SVR after all this...

[SkipinCA]

I am UND again.  My hopes are up.  To refresh everyone, after being UND and TMA negative from week 4 through 20 (of 24-weeks tx - I'm geno 2b), and then suddenly showing VL of 773 at week 21 and and 885 at week 23, I upped the dose of Riba from 1000 to 1200 on 1/7 and again to 1400 on 1/10 and then tested again on 1/21 and now am UND<50 again.  My other counts from this morning's CBC:  WBC 3.4; ANC 1.64; Platelets 175; Hgb 12.4; Hct 36.7; AST 27; ALT 26.  

My doc wants me to continue now at 1400 riba and 180mcg pegassys for at least another 12 weeks.  I'm thinking if I can tolerate this and after hearing from you all I should go longer than 12 weeks.  We've talked about precerting procrit if needed to help take me through to the end of tx. The fact that I'm UND again - do my chances of a successful SVR increase?  I believe it has been said that even if this was not a breakthrough earlier, my chances are diminished for success.  
Thanks,
Skip

[SkipinCA]

Thanks for the well wishes and for your input.  It is an interesting journey and it is nice to know I'm not alone.  So many of you have gone through so much!  It is an inspiration to me, especially when the going gets tough.  I keep all of you in my thoughts and prayers.
Skip

[sfbaygirl]

Good for you. Keep up the good attitude and keep on posting here. You will learn a lot. Get copies of those labs and keep up with the studies. They will bode well for you.  You have gotten some good advise. Some Dr's don't know some of this stuff, believe me, I had one that didn't.  So be well and good luck on your journey.

Linda

[SkipinCA]

Thanks again for your help and comments. The <50 was what I was told early on and I just never questioned it further.  I've relayed the info I was given to my docs so they have it.  At least, I'm comforted knowing it is a sensitive test.  I will be taking a good look at my tests from now on.  Hoping for smooth sailing through July.  
My best regards,
Skip

[jmjm530]

If I understand what you said your doc said, then the Bdna (a quantitative that gives a number) reflexes to a TMA Qualitative which just says whether you're UND or not to a sensitivity of 10 IU/ml, which is considered a very sensitive test. That still doesn't explain the "<50", so maybe something is getting lost in translation and why it's always a good idea not only get your own copies of all blood tests but to also spend a little time/research in desciphering them, as we've seen incorrect interpretations here, even from treatment doctors or their NPs. I think "Willing" and I are pretty much in agreement in regards to uncharted waters, but I also think the 24 weeks xtra your doctor suggests is a reasonable strategy based on what happend and your genotype. Also, unlike some of the studies Willing mentions, you appear to have been underdosed with riba which I view as a positive in terms of future response.

All the best moving forward,

-- Jim

[willing]

good to hear you're bearing up well. I can understand your frustration but as others have pointed out it's important to understand that *no-one*, your Dr included, has any reliable idea of what your outcome odds are and of how different dosage/duration changes may affect the outcome.

Clearly something unsual happened that resulted in the development of viral resistance after rvr at 4 and und through 16; it's unfortunate that it was not possible to gather any information about that tx-resistant virus. The sensitivity of your current tests is pretty much irrelevant  given you were recently as high as 885.  Information about continuing tx in the face of breakthrough is scarce.  You might want to look at:

http://www.ncbi.nlm.nih.gov/pubmed/17253142

the point there was that, in the presence of flucutating vl and breakthrough, the only two patients who got to svr did 48 after  confirmed UND. These were 1s, so there's no way to gauge how it applies to 2s. There's also no way of knowing whether  the current  viral dip is really due to the increased rbv or simply to vl fluctuation (breakthrough is not permanent).

The overall point from win-r was that neither weight-based rbv nor duration longer than 24 had much impact on g2/g3 svr odds  but if you're going to push forwards with soc there's not much in the way of alternatives. Kalio's successful, long-term, approach may be worth looking at. Take care!

>After tx if one reaches a SVR, and then relapses, is there ever
>the possibility for the body to clear the virus on its own
>after tx?
I've seen this reported twice since I've been around here (nygirl  is one). Whether the 1st tests were false positives or whether the body successfully cleared remaining virus on its own is a good question...

[sfbaygirl]

That sounds about right. If your TMA is neg and is sensitive to <10 IU/ml you are in pretty good shape.  Yes, if you had a VL above 615 you would have gotten that number, but since it was lower it does trigger the lab to go to a more sensitive test.  Mine only went down to <50 and was triggered at <75, so my tests were not as sensitive as yours. My ins wouldn't pay for the tests Jim mentioned, so I went with these.  Going down to <10 is pretty good, means only under 10 little virons could be running around!  I still would consider extending 24 weeks.  Good luck.

[SkipinCA]

Just realizing that if TMA neg. means <10, then when I had the virus come back, it only needed an amount <10 to do so.  Am seeing the importance of the more sensitive tests.  After tx if one reaches a SVR, and then relapses, is there ever the possibility for the body to clear the virus on its own after tx?

[SkipinCA]

I got hold of the immunology dept. and was finally able to get an answer about the "HCV RNA by BDNA" and TMA testing they do for me.  I'm sure you all can explain this to me better, but I was told that the HCV RNA by BDNA gives an actual number, i.e. <615, and if that happens it triggers the TMA test which is associated with the name Siemens (or Bayer).  The guy said this TMA test does not give a specific number but is sensitive to 10 IU/ml.  So a TMA negative means <10.  Have I got that right?

I asked about the two other tests mentioned (the Quest Diag. and LabCorp tests) and he said he didn't think they can send out for those here.  Hopefully, I'll be ok with the one they are using for me.  Are the other tests just available in certain areas? Curious.
skip

[sfbaygirl]

I think you are correct. I know that I thought I was clear at week 12, when my PCR was clear at 75IU/ml but detectable above 50IU/ml. We went round and round about it, but turned out that that small amt of virus was alive and kicking and I ended up relapsing.  So a very sensitive test is very important as that 615 UND test could have 614 little virons running around live and kicking!  

[mar148]

I think what is the concern is the at under 615 is a high cut off detection and could mean you were really detected if you had been tested by a more sensitive test that went down to 10 or 50, meaning you could have identified the dosage issue earlier.

[SkipinCA]

Thanks Jim.  I checked my Hgb throughout the changes in riba dosage (see mine to Proactive above) and there really hasn't been a whole lot of fluctuation, which I guess is a good thing.  Also, I just earlier today caught an email from my doc that, whereas earlier I was told 12 weeks by the doc's fellow, I should instead plan on another 24 weeks starting from the date I was UND, which was Jan. 21, which means I'm going through July 11.  That answers my question about whether 12 weeks is long enough! She evidently things it is not. :).  By then I will actually have done 50 weeks total.
So I guess I'm in for the long haul.

I have brought up the HCV RNA test question and will check my records to see if I can
find an answer about the test sensitivity.

You mentioned that I'm "in a sense starting back in the pack (slow response)."
Doesn't it count for something the fact that I was UND and TMA neg. from weeks 4-16 and then over three tests went from <615 TMA Pos. to 773 and to 885, and then with the increased riba for two weeks and another test putting me UND, again <615 TMA Neg?  I guess I'm not clear on what determines a slow response.  Seems not quite clear cut in my case.  
Skip

[sfbaygirl]

I agree with Jim about the uncharted water here. We know that if we don't clear by week 12 we need to tx longer, but breakthroughs are rare and not enough known to say whether or not it will work to go longer and harder. If it were me, I would not want to give up all the weeks I put into tx and would go through the long haul...meaning 24 weeks for your geno after UND. If you were a 1 or 4, I would say 36 weeks after UND.  So that is my opinion and as it is uncharted,  that's what I would personally do.  Good luck!

Linda

[SkipinCA]

Thanks.  I'm finding it pretty amazing how my body seems to be adjusting to this stuff.  My hgb was 16.7 at the start (26 weeks ago) and went down to 11.9 at week 4, then back up to 14.6 at week 14.  Since going to 1400 from 1000 riba on Jan. 10, my Hgb has only gone from 13.4 to 12.4.  Nice to know there are others out there tolerating larger dosages... Hoping I won't need to go more than 1400, but am more comfortable with the idea if necessary. Skip    

[jmjm530]

Skip: It seems your suggesting that getting through another 24 weeks on 1400 without a breakthrough should be good enough.  I just don't want it to be that this fails because I haven't taken enough dosage to take care of things.
--------------
I wish I, or anyone else could have an answer for you here. As stated, you're somewhat in unnknown territory given your viral load curve. Certainly 24 weeks more would potentially offer you a better chance than the 12 more your doc suggested, but in a sense both numbers are being pulled out of a hat as it would be hard to match study data to your stats.

You said, earlier "keep thinking the longer the tx, the more chance of collateral damage in my body.  Now that 1400 seems to be doing the trick, would there be any benefit to upping the dose to 1600?"  -- and that is true, both for tx length and even upping the riba.

If you had signficant liver damage, I'd feel more comfortable cheer-leading you on with higher doses and longer times, but you have very little damage, so it's a difficult call and that's maybe why your doc is taking a more conservative position -recommending only 12 weeks and holding the riba -- because he wants to minimize the risks of treatment.

Yes, in general, more drugs, longer treatment -- the better your chances, esp with slow responders -- but also the greater the risks. Wish I had an easy answer.

-- Jim

[jmjm530]

Given you weight, it appears you were not on weight-based ribavirin to start out with and therefore underdosed by that standard. This may have been the reason for your slow viral response.

Right now you are on weight based which is good.  As to upping the ribavirn further, probably not necessary assuming you are UND, but given that you're in a sense starting back in the pack (slow response) it could be a reasonable decision if you titered up gradually and monitored your hgb on a frequent basis.  Certainly no science, but what might be of interest would be what your pre-treatment hemoglobin was, how it changed per different riba doses and how that compared to your viral load at various points in time.In this scenario (more riba), it would be more likely that you would need Procrit (epo).

My point earlier with epo is to get the rx and paperwork done now, so it will be ready when needed. I got epo the first time at hgb 12.8 -- so no, there is nothing written in stone as to when your insurance company will prescribe epo. It depends on both your insurance company and your doctor. If your doctor writes it, then often it will go through.

Not sure what test they are using, but sounds like a combination Bdna (not very senstiive) which reflexes (automatically triggers) a more sensitive test. You say "TMA" but TMA's are usually more sensitive than 50 IU/ml and it should say that right on your lab report which you should have a copy of. As stated earlier, given your viral response, I'd ask for the most sensitive tests possible and have them monthly.

So, unless you're certain the current test goes down to 5 IU/ml -- not 50 IU/ml -- (again check your lab report yourself and/or ask doctor and lab)  then, again,  I'd ask for either of the following tests, monthly.

1. Quest Diagnostics's "HCV RNA TMA QUALITATIVE" (sensitivity 5 IU/ml)

2. Lab Corp's " HCV NGI ultraqual" LC#140609" (sensitivity 2-3 IU/ml) (make sure to use the LC test number if doing the LabCorp test).  

[Proactive]

welcome to the riba dosage increase club!!! (lol)....I also started at 1200mg (165 #'s), went to 1400mg @ week 8, and onto 1600mg at week 12-13...cleared prior to week 18..Over time, the additional riba has worn me down, but hgb has stayed above 11...I really didn't notice any additional "acute" sides from the extra riba...and...I have even accidently double dosed the riba at least twice during tx (took morning dose twice-forgot I'd already dosed, total of 1600mg for breakfast (g))..of course, I still took my evening dose....no real sledgehammer effect...
best of luck....
PS: Bill1954 is on 2000 mg/day...not sure of his weight, but from his pic, I'd guess we weigh about the same...(around 165-170)

[SkipinCA]

My original VL was 2,387,610, Biopsy pre-tx said grade 1, stage 0 "mild steatosis" - not sure exactly what that means, but was told no fibrosis and that everything was "pink" and that it was a great result.  I weighed 238 at beginning tx, and am down to 215 now.  Since I'm UND again, I want to make sure to give myself the chance to stay there so am definitely not going to lower the dose.  I seem to be tolerating things pretty well - no bad sx except fatigue mainly.  I don't feel any different really on the higher dose.  I'll definitely do the procrit if necessary.  I'm told most insurance companies won't approve until your Hgb is under 12 so as soon as that happens we will precert.

Jim, if I'm still managing ok after 12 weeks I'm definitely going to suggest continuing longer just to give myself the best chances.  It appears I don't have any liver damage if my biopsy results (from 2003) still hold true, and I've been reassured that the tx, while stopping the virus, is also helping my liver stay healthy rather than causing it to be weaker.  It has been a worry.  I keep thinking the longer the tx, the more chance of collateral damage in my body.  Now that 1400 seems to be doing the trick, would there be any benefit to upping the dose to 1600?  I doubt my doc will want that, but I'm amazed at how little difference I feel going from 1000mg to 1400mg.  I hardly even have fevers any more - just fatigue really.  It seems your suggesting that getting through another 24 weeks on 1400 without a breakthrough should be good enough.  I just don't want it to be that this fails because I haven't taken enough dosage to take care of things.

Re the VL test, I'm told the HCV RNA test is the most sensitive available and it's the same one they've given me throughout tx.  On my hospital statement it reads "HCV RNA by BDNA Quant" and my standing order says "HCV RNA by BDNA."  I'm told the TMA negative means less than 50 copies or some such, or is that less than 5 in other med language?  Is that comparable to the ones you mention?  I will mention these to my doc to see if they are the same.

Skip

[jmjm530]

That's much better news Skip, but your viral flip-flop sort of puts you in uncharted waters in terms of how long to treat.

I'd think you might want to try another another 24 weeks if you can tolerate, esp if you have significant liver damage. Also, given your mecurial viral response, I'd ask for monthly viral load testing and use one of the most sensitive tests available such as Quest's HCV RNA TMA QUALITIATIVE or LabCorp's ULTRAQUAL. If you for some reason, the virus raises its ugly head gain, I'd consider stopping.  Also, keep a keen eye on your hgb and how you feel. Since upping the riba may have done the trick, you don't want to have to cut back which means adding Procrit (epo) at the earliest sign of trouble. Keep in mind it takes epo 2-4 weeks to kick in, so you might want to get an rx in hand and start working the insurance process now, even if you may not need it.

BTW what test did they use this time for your UND and what was the sensitivity.

-- Jim

[mar148]

Well is seems like you have a great doctor.  From what I have learned you new strategy seems like a good strategy to attain SVR.  What was your starting VL and liver fibrosis level?  What is your weight?  upping the riba and extending seems like a solid process.