Am I grasping at straws?

[Marc1955]

So I just heard from my treating physician that I didn't clear at 24 weeks. I'm 51 yo, type 1A, fibrosis 2/2 on biopsy. My original viral load was 900,000. I made the 2 log drop at 12 weeks. At 24 weeks that count came back as 50 iu/ml.

Based on information I read on this board, I decided I didn't want to throw in the towel just yet. My physician, a Heptology Prof at the U. of MD is willing to let me go three more months with monthly tests to see where we are. I'm holding out the hope that I might still clear soon and then extend the treatment to 72 weeks to get SVR. That seemed to be the approach that many on this board would take.

Thoughts? It's very tough to throw in the towel after you've battled with the treatment for six months. If nothing else, this extra time will give me a chance to adjust to the new reality.

[smaug48]

"meanwhile, hopefully no one will extend (or not extend) based solely on our opinions here. You really need to dig up all pertinent full-text studies and discuss with a competent liver specialist."

I completely agree!!!!

smaug

[jmjm530]

Let me just clarify the above by saying that, yes, some studies were "framed" to exclude null (detectible at week 12) responders -- but do recall reading at least one study which followed null responders through 72 weeks. I'll do my best to find it.

[jmjm530]

No, I don't think so. I'm almost positive the study results suggested very little chance of SVR if still detectible by week 24, even with extension to 72 weeks. I'll try and dig up something more specific to that -- meanwhile, hopefully no one will extend (or not extend) based solely on our opinions here. You really need to dig up all pertinent full-text studies and discuss with a competent liver specialist.

[smaug48]

Jim:  Right!  It wasn't the study results that said people shouldn't continue tx if they didn't und by week 24.  The doctors who framed the studies pre-decided to not continue tx for people who didn't und by week 24.

Za:  Thanks Za!  The risks of such a long treatment really concern me (as well as being a major bummer in terms of quality of life), but given the risk of going to stage 4 while waiting for something new, it seems like extended tx is the way I should go.  Hope your trip back to normalcy is going swiftly!!

smaug

[jmjm530]

Note the last sentence in Berg,here: http://www.ncbi.nlm.nih.gov/pubmed/16618403

I think u will find that all the 72 week studies have similar if u read the full-text, as these studies all refer to "slow responders" which is usually defined as detect at 12 and UND at 24. Detectible at 24 is considered a null (non) responder for these study purposes and no study (other than the one you presented) suggests they should treat beyond 24 weeks.

[zazza]

88 weeks, that is a brave decision, but a wise one I think. Good luck to you, Smaug!

[smaug48]

I pretty much agree with everything you wrote, except for:

"with previous studies that showed significantly less SVR rates, in the sub-population who was detectible at week 24 and treated for 72 weeks. Unless I'm missing something, how can you have almost no chance of SVR if detectible at week 24 and treat for 72 weeks."  

I haven't seen a study where not getting und by week 24 but treating 72 weeks resulted in almost no chance of SVR.  

If I read them correctly, the studies I've seen automatically dropped people if they didn't get to und by week 24, which I presume was based on previous studies where people who got und after week 24 but only treated for 48 weeks had a 2% chance of SVR.

If you know of a study that says differently, could you please post?

In this Arase study, it seems that there wasn't enough statistical support to make recommendation for length of treatment for super late responders (und week 25 or later).  In the conclusion they only recommend:
30 weeks tx beyond und for RVR (und by week 4)
40 weeks for EVR (und between weeks 5-12)
60 weeks for LVR (und between 13-24).  

So I'm guessing it can't be said with certainty what the SVR chance is for someone who goes und between 25-48, but certainly it is higher than 2% if they treat for >60 weeks beyond und.

Marc and I are almost in the same boat right now.  I just became und at week 28.  But I am "at least stage 3" according to my doctor, so I am choosing to continue, and will do 88 weeks of tx and taper afterward since I am tolerating tx fairly well.

I completely agree with you about the risk/reward equation with regard to doing such a long tx.      In my opinion, Marc has an option of stopping, whereas I don't.  But that's just my opinion.

smaug

[nygirl7]

ps it wasn't until after week 24 that my thyroid ran into trouble...........and it wasn't until about week 50 or 60 that I got serious skin issues.  The longer the time you do the interferon the more risks you are indeed taking with your health. Not that it wasn't worth it to me of course but my odds were good. It's a big risk to go long and not even have a 50/50 chance that we all start out with (let alone practically any chance).

Just something to think about - of course if you do decide to go for it you know we will support you heart and soul!

debby

[nygirl7]

I would ask my doctor to retest that number immediately.  If in fact you are detectible - going for 72 weeks wouldn't even be a viable option because you aren't UND yet and don't know when you might really be.  The 72 weeks is for people who are UND.  It's hard to say throw in the towel but the odds as far as I've SEEN with people in here (not basing anything on one new study) aren't good.

I treated for 72 however I was UND at week 24.  If I had not been my doctor wouldn't have considered letting me continue onwards.

So I would advise in my personal opinion retest - see if you are UND right now and if not then take some time, regroup and start over.  

But that's a hard pill to swallow - thank God you have time and are only a stage 2.  

[jmjm530]

On a second read, it appears that the "27%" SVR rate for SLVR's was for those that treated only 48 weeks and the 100% SVR rate was for those who treated 90 weeks.

Small sample aside (9 patients in the extended SLVR group) 100% SVR (with 90 weeks) is quite dramatic, however, one could bring that number into question when examining the 27% SLVR rate in the 48 week group which seems quite at odds with previous studies that showed significantly less SVR rates, in the sub-population who was detectible at week 24 and treated for 72 weeks. Unless I'm missing something, how can you have almost no chance of SVR if detectible at week 24 and treat for 72 weeks but have a 27% chance of SVR if detectible at week 24 if you treat for 48 weeks? Perhaps some of the difference is bridged with the current study eliminating those who become detectible between weeks 24 and 48, but it still brings some of these figures into question and encourages more examination against prior studies.

-- Jim

[jmjm530]

First, thanks for posting this new study.

Using study criteria, this would put "Marc" in the SLVR (super late virological response) group, assuming: (1) He is actually still detectible on re-test/re-evaluation; and (2) If so, that he becomes UND before week 48.

For discussion's sake, let's assume that Marc is still detectible at week 24 and becomes UND at week 30. The study seems to  suggest that he would have "x" chance of SVR (non-relapse in their words) if he continued treatment for 60 weeks beyond the point of being UND. That would be a total tx period of 90 weeks or a bit shy of two years.

As to "x", I'm a bit confused if his chances of SVR would be 27% or 100%, as the figures appear to be presented both ways. Perhaps the lower number includes drop outs, not sure. Again, for discussions sake, let's say his chances would be 50-50 or even 75-25, and I'm really just guessing here. The question still remains should someone with only stage 2 liver damage treat for close to two years (an additional 1.5 years in Mark's case) for a decent chance of SVR? Personally, I wouldn't, but that's just one person's opinion.

Thanks again for posting, and I confess to going through the study rather fast so please correct me for any mis-statements. It's interesting that in a sense this study is sort of a sliding scale "Drusano" formula, which had been used in the past, at least by my liver specialist. Not based on any study per say, but on his clinical experience.

It certainly appears to offer hope to those who are still detectible at week 24 and feel that the risk/reward equation (factoring in the level of liver damage, etc) of treating 90 weeks is worth it, cause that's a lot of exposure to these drugs when the alternative is to cut your losses and wait for the newer/shorter duration treatments to hit the market.

Also, while again hopeful, anyone using this study for a tx decision should carefully compare this data (including patient population, etc) against previous studies and bring all to a good liver specialist (hepatologist) for discussion and decisions.

-- Jim

[smaug48]

"You would need at least 72 weeks total to have a decent chance of SVR, but that's based on studies where the patient was UND at week 24. In your case, it's hard to know how many more weeks you would need and remember, no studies to show if it would make any difference anyway."

There is a new study that shows how many weeks should be done and it WOULD make a difference.  Please see:

Link fulltext:
http://www.jstage.jst.go.jp/article/internalmedicine/47/14/1301/_pdf
or  http://tinyurl.com/5efhmy

smaug

[jmjm530]

Actually, should you continue, it would not be another six months". You would need at least 72 weeks total to have a decent chance of SVR, but that's based on studies where the patient was UND at week 24. In your case, it's hard to know how many more weeks you would need and remember, no studies to show if it would make any difference anyway. The basic tenant in medicine is "first, do no harm".

[jmjm530]

Assuming you were actually detectible at week 24 on re-test, Im not sure why you're saying you want to continue based on what you've read here in this forum.

Studies suggest that if you're still detectible at week 24, your chances of SVR are very close to zero, and my recollection is that most here have posted such. This also appears to be the recommendation of your treating doctors so please do not use any information/speculation here to go against that unless it is persuasive, i.e. have facts and studies behind it. This is especially true since you do not have significant liver damage and therefore the risks of treatment with a very poor treatment outlook tilt  the risk/reward equation toward cutting your losses in my opinion. The fact that you have invested six months does not mean you have to subject yoursefl to another six months of treatment with very little chance of success. Please re-test and then get another professional opininion from a liver expert (hepatologist) before deciding to continue for another six months.

-- Jim

[Bill1954]

Thanks for the reply; I wasn’t sure where you were on the knowledge curve regarding this disease, but it appears you are fairly familiar with this landscape.

OK, there goes my theory; I just wanted to make sure some RN or NP wasn’t misinterpreting results. I would still request another test; you have nothing to lose and tons to gain by this. Besides, serial NAT testing results are almost irrefutable.

We’ve had a number of patients report very low viral titers (and I’m referring to post Tx data) that when questioned and re-tested, resulted in negative RNA. This actually happened to a gal in our local HCV support meeting; *twice* she had extremely low VL results interspersed with additional negative RNA. It took her doctors almost a year to sort thing out and pronounce her SVR.

I realize this is in reference to post treatment data, and doesn’t accurately reflect your situation; never the less, I would discuss retest with your doc.

As you know, you will also want to address the issue of late viral response. For what it’s worth, during a previous treatment attempt, I had a slow response, and didn’t achieve a 2-log 10 drop at the 12 week juncture. Working closely with my doctor, we aggressively increased my riba dosage and extended treatment to 56 weeks to give me 36 weeks of continuous UND status (I eventually cleared to <50 at week 20). In my case, the end result was relapse at 30 days post Tx.

It might make sense to regroup; and come up with a plan that takes that initial VL down in a big hurry off the get-go; aggressive dosing with SOC is one scenario that comes to mind.  

Weigh all the options carefully, read as much as you can stand :o), and keep an open dialogue with your doctor.

My best to you and your outcome—

Bill

[Marc1955]

Bill – Here is the verbiage from the test. As opposed to other tests, it detects down to 10 IU/ml:

 Hepatitis C Quantitation: 50 IU/mL 
   
 HCV log10  1.699
   
 Please note: 
 
   This test measures HCV RNA in International Units (IU) per mL using real-time Polymerase Chain Reaction (RT-PCR) technology. It quantitates HCV RNA from 10 to 100,000,000 IU/mL.  The assay was developed and its performance characteristics were determined by LabCorp. It has not been cleared or approved by the  U.S. Food and Drug Administration. The FDA has determined that
 such clearance or approval is not necessary. This test is used for clinical purposes. It should not be regarded as investigational or for research.

When I spoke to my physician one reason I could convince him to let me proceed is that if I had taken a qualitative test with a cut-off of 50, it's quite possible the result would have come back as negative.

[meki]

I am a 3 a Geno === Most people say that if you don't clear by 4 weeks or go und by 4 weeks - then you have hardly any chance of clearing.

I didn't clear at week 12 - week 14/16 I was UND.

I am an unusual case.

So --- If I can do it - there is always the possibility that your viral shelf life is like mine - maybe it just needs more than half the regular amount of TX to bring it down enough.

FOR you that would be week 26 - 28... Maybe even 30.

So wait - don't throw in the towel.

If necessary - pull until the 72 week mark.

If it can be done - and SX aren't horrid --- then do it if you can... At least I would.

Because I WAS NOT GOING TO TREAT AGAIN.

My sides were horrid.

But I have SVR now.

Meki

[smaug48]

The odds of SVR go down if you don't clear at 24 weeks, but they can be much higher than 2% if you extend treatment, depending on when you get to und and how long you treat.  See a recent thread for a new study that is very important for slow responders:  http://www.medhelp.org/posts/show/575996

HCA makes a good point that because you are stage 2, waiting for Teleprevir is a viable option.  If you decide to stop treatment now, you might consider researching supplements you can take to keep your liver from getting worse until you treat again - lots of good info in older MedHelp threads from Hepatitis Researcher.  You can start by taking a look at Gauf's profile.

Good luck!

smaug

[Bill1954]

I wholeheartedly agree that a re-test is in order; I’d also question the interpretation of the existing test. Do you have a copy of the latest VL test results? The lower limit of detection for many PCR tests is <50; in other words, you could possibly be HCV RNA negative right now, if the test results have been misinterpreted. If the hard copy of the labs is available, type the pertinent info into the forum, and perhaps we can figure this out ourselves.

I see very little harm continuing the meds for a short time, until this can be sorted out. Based on what you have provided so far, something sounds wrong.

Good luck and let us know—

Bill

[copyman]

first thing i would do is re-test. that VL is very low and could be a false-postive.  Like HCV said the odds of clearing the virus go way down if still detectable at 24 weeks. Something like 2% chance even with 72 weeks. If you do a re-test and are still detectable you should stop and either get into a non-responder trial or wait for the new drugs coming out in the next few years. good luck with whatever you decide.

[HCA]

Positive viral serum (however low) at 24 weeks is bad news-even with extended treatment.The odds of SVR are very low because you are likely to have an interferon resistant mutant (wild type variant) which will cause relapse after the cessation of treatment.
The good news is that at stage two fibrosis you can wait a couple of years for Telaprevir which all the data indicates will in combination kick the xxxx out of your virus before it knows what's hit it!

[rita863]

Nygirl may comment you on this she has treated for 72 weeks and now is SVR,,,Bill is also someone who treated for 96 weeks....so i would not through in the towel!

[Texas714]

I'd just like to say, Don't "throw in the towel".  You may have to re-group and come up with Plan B and maybe Plan C.  It sounds like that is the path you are on.  I'm sorry you didn't have better results this time but you are in good shape with a 2/2 and have lots of possibilities ahead in your future.  Good Luck what ever you decide to do!