Confusion about UND

[jankar]

What does UND really mean?

I had a result of UND<15 at week 4, someone else a UND<10 at week 4.  Is this result sensitive enough to base a decision on 24 weeks or 48 weeks?  Another suggested we needed weekly or daily tests in the first four weeks to make a decision, another suggested that those results are still detectable and if present at week 12 in the same levels, needs to result in 72 weeks treatment.

Thanks for all the research responses - I am particularly interested in results for 1b on Pegaysus 2a and Ribavirin as those results differ I think to the results from all Geno 1's and Pegysus 2b

[epiphiny]

Thank you for explaining the use of 'statistical' in this context as I did wonder about it but decided to take the percentages at face value.  Yes, I do know there is no 100% SVR guarantee but if that's the case it bugs me that they report things back in that format.  Anyway, I am debating semantics and that's not what we are here for...

The thing is, I also wondered about the long term risk of IFN & Riba exposure and whether the extra time exposed is worth the (slightly) increased chance of SVR as I was originally scheduled for 24 and pushed to go for 48.  I am now at week 35.  I don't regret that choice in any way.

I think one can read all the studies, and process all the info, weigh the pros and cons and it will still come down to an emotional decision, 'gut instinct' if you will, and a big dollop of courage and fortitude..

I did not think I had the courage and fortitude to be able to handle another treatment failure without the knowledge that I had done EVERYTHING I could in this battle and so, I had to press on...  Luckily, I am treatment-experienced and suffered no long term effects from my previous tx (other than the loss of my long golden locks but that's just vanity) so I come with a different perspective.

You're right, nothing is set in stone and who knows what factors come into play with study participants success or failure but this decision is based on more than the statistics.  It's based on circumstances, willpower, emotional stability, individual tolerability to the meds and so on...

[orleans]

There is no "statistical" difference here. One could do the exact same trial and come out with a reversal of these numbers. There is no such thing as 100% SVR in today's world. Does it happen? Sometimes, the very same trial may only have 80% svr next time. jerry ps just how much gambling is a thyroid, RA, chronic fatuige etc., etc., etc., worth. Long exposure to IFN/RIBA does have it's on serious risks. This is why one of the main goals of the new drugs is to shorten tx.

[epiphiny]

"Stated another way, relapse rates after completion of treatment were statistically similar in the low baseline viral load group, whether they were treated for 24 weeks (3.6%) or 48 weeks (0%)"

There is a world of difference between 0% and 3.6%, especially if you are one of the 3.6%.

I know I am repeating myself but as per the above quoted study 48 weeks is offering 100% and 24 is not.  It's a no brainer to me but I am not a gambling woman.

[jmjm530]

A couple of studies for you to discuss with your doctor:

(1)

"...This study demonstrated that a shorter course of 24-week peginterferon alfa-2a (40KD) plus weight-based ribavirin 1000/1200 mg/day was as effective as a standard 48-week course in patients chronically infected with HCV genotype 1 who had a low baseline viral load (LVL) and achieved an RVR at week 4..."

http://www.natap.org/2007/AASLD/AASLD_44.htm


(2)


"...For 52 patients with low baseline HCV RNA viremia (< 400,000 IU/mL) and RVR, however, the 24-week arm had an SVR rate of 96.4%, which was comparable to the 100% rate seen in the 48-week arm...Stated another way, relapse rates after completion of treatment were statistically similar in the low baseline viral load group, whether they were treated for 24 weeks (3.6%) or 48 weeks (0%).

http://www.hivandhepatitis.com/hep_c/news/2008/070408_a.html

[jmjm530]

my ALT's and AST's dropped to within normal range for the first time in years during the first four weeks but have since gone back up to just outside normal.  Does this mean anything?
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Most probably no meaning,  as this frequently happens with no consequences in terms of SVR. The enzymes should drop back to normal once the treatment drugs are stopped if not before. That said, the prudent thing is to test viral load monthly during treatment to make sure you remain UND during treatment. The only number that really matters is your viral load.

-- Jim

[jankar]

Hi - that is what I am going to do exactly.  It has been great getting all the different opinions as I can become clearer about what questions to ask.  Some of it is conflicting but day by day I am beginning to sort it out and I have a lot of time left before Week 24.

Another thing - my ALT's and AST's dropped to within normal range for the first time in years during the first four weeks but have since gone back up to just outside normal.  Does this mean anything?

[jmjm530]

That's amazing the NZ docs are actually considering shortening treatment given that they are generally so protocol based here.
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My understanding is that 24 weeks IS the protocol now in Europe for geno 1's who demonstrate both low pre-treatment viral load and are UND at week 4.

Jankar,

You have received a A LOT of advice here, some of it conflicting, and a lot of it speculation and opinion. The shorter 24-week treatment is an actual protocol  based on several studies showing near identical results for 24 versus 48 weeks. The fact that many here in the U.S. are unaware or not using that protocol does not mean it's not valid. Why don't you dig up the studies, bring them to a hepatologist (liver specialist)  and discuss before making any decisions.

-- Jim

[geterdone]

The major difference is I'm on familiar ground, whereas in the first months, tx really put me in my place and I didn't like that one bit.
*****
Got a good chuckle out of that line. Yup, those first couple of months are a real eye opener, lol.

jankar, Try not to stress too much about the decision, you’ll do what is right for you.

jim, you are the master of your craft.

jasper

[epiphiny]

Ooops, sorry, misread your journal entry!   I am sure you will make the right decision...  

That's amazing the NZ docs are actually considering shortening treatment given that they are generally so protocol based here.  Then again it certainly would be a bonus to the national health budget if more people treated for less time, so long as they don't have to do it twice.  And then maybe they (Pharmac) could consider treating the 40-odd HCV3 people left in NZ who are currently the only ones deemed 'not sick enough' to receive treatment.

Oh, how I wish for an ideal world (read Health System) and the ideal HCV treatment that guarantees SVR for all...

[portann]

Those are really great baseline numbers!

Good luck on your decision. I'd be torn but 24 is so tempting. It's the concept, the prospect, the escape route via 24.

I remember when I reached week 24, I thought hard about how wonderful it would have been to stop at that point.  My husband felt awful to see my life curtailed and dazed I was 'only' half-way, after so long.

Part two, though, goes by, week by week.  Forty-eight weeks, a day at a time. Except for a couple of episodes, it's been not too bad, as far as it goes. The major difference is I'm on familiar ground, whereas in the first months, tx really put me in my place and I didn't like that one bit.

Best of everything.

[jankar]

I did have two vl tests prior to treatment and it was offered as a possible option to shorten treatment depending on how I went.

Test 1 5 Sep 2008 HCV Viral Load Log 5.48, 302359
Test 2 29 Sep 2008 HCV Viral Load Log 5.39, 245122
Began Treatment 3 October 2008,
Test 3 29 October 2008 HCV Viral Load Log <1.18, <15IU/mL

Roche COBAS Ampliprep/Taqman HCV test.

Epiphany, I have not actually decided to do 48 weeks, just doing my planning around it while I take the time to read and think about it.  If I plan around it it becomes not so overwhelming trying to decide stuff.

Thanks for all the responses on the thread, they certainly have covered all the issues I had thought of very thoroughly.  great dialogue and discussion.

[jmjm530]

Gett: Yes, <15 is UND if that is the lowest sensitivity of that particular test but is it enough for a lay person to make a decision to treat 24 instead of the 48 week SOC and chance the difference between success and failure, no.
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Sure it is. It doesn't mean that the answer is necessarily to shorten treat, but that is one reasonable decision between doc and patient if the patient meets the other requirements such as low pre-tx viral load.

Get: The people in the research in which the studies were compiled were monitored very closely during the course of their treatment which is not fully available to the lay person and is not the main stream of treatment given the research presented as of yet.
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I'm not sure what special type of monitoring you're talking about. The studies are specific as to what criteria determines a shorter course option. These criteria are available to docs and patients and in fact have been turned into guidelines by many docs. The European Union and Berg comes to mind in terms of recommending a shorter tx option in selected cases. Individualized treatment doesn't just mean extending if detectible at 12, it also means the option to shorten if certain criteria are met. I certainly respect your opinion not to shorten, but it really has nothing to do with any special way people in the studies were monitored or treated.

[geterdone]

Yes, <15 is UND if that is the lowest sensitivity of that particular test but is it enough for a lay person to make a decision to treat 24 instead of the 48 week SOC and chance the difference between success and failure, no. The people in the research in which the studies were compiled were monitored very closely during the course of their treatment which is not fully available to the lay person and is not the main stream of treatment given the research presented as of yet. Someday it will be, but would I be willing to take a chance even with a low viral load, without hard evidence and statistic showing there were more SVR than not, NO. Heck, I was not satisfied with the tests down to <2 and I am still not, even coming up on the one year.

You see, I was not trying to give all the research mambo jumbo and small statistics surrounding the 24 verses 48 weeks, just some common sense to someone who is, as well as my self, less knowledgeable about the research and the data with in it to put myself in a stacked deck of cards in favor of the virus and stated my opinion to that end. Nor was I challenging you or anyone else of their opinions on the subject other than the fact that almost everyone posting to this thread has completed their treatment within the SOC, for the most part, given their particular geno type, liver damage and individual viral loads which dictated the SOC for them or group.

I will ask this, are their statistics showing how many people achieved SVR in this particular 24 week group, that being, Low viral load, UND at week 4 or sooner, little or not liver damage. Can these statistics is be produced.

Not sure about the tone of the reply here, so hope no offence is taken because of the full moon.

jasper

[Proactive]

"Another suggested we needed weekly or daily tests in the first four weeks to make a decision"

Blame me, I brought up the subject, a bit hypothetical mind you, certainly not something most mear mortals can accomplish though..(g)

But to the point, if it was me, and I met the reduced 24 wk from 48 wk treatment criteria, I sure would like to have the additional knowledge gained from high frequency testing in the first 4 weeks. I say this because of the addition svr predictability knowledge that would be gained when looking at biphasic viral decline
Some believe the first few days can be a very good predictor through viral kinetics.

"summary. It has recently been shown that upon initiation of interferon (IFN) treatment there is a biphasic decline in hepatitis C virus (HCV) RNA levels. In preliminary results, the rate of second phase viral decline has been shown to be an excellent predictor of treatment response. In this analysis, we determined whether the first phase viral kinetic parameters affected the rate of second phase viral decline. We also assessed whether first phase viral kinetic parameters could be used to predict treatment response within 24 h of initiating treatment. This study is a retrospective analysis of two completed studies from which detailed kinetic data were obtained in patients infected with genotype 1 HCV. In both studies, viral levels were measured frequently over the first 24 h, allowing the determination of IFNs effectiveness in blocking viral production and the viral load at the end of the first phase (v1). The second phase decline slope was calculated by log-linear regression on measurements of serum HCV RNA during days 2, 7 and 14. In study one, sustained viral response (SVR) rates were obtained, allowing the determination of the first phase's predictive power for SVR. Logistic regression and fisher exact tests were used to analyse data. In study one, no patient achieved SVR without an IFN effectiveness greater than 98% and a V1 less than 250 000 copies/mL. When V1 and IFN effectiveness werecombined to predict SVR, a negative predictive value= 100%, positive predictive value=71% and accuracy of 95% was obtained after only 24 h of IFN treatment. Both studies illustrated strong correlations for both IFN effectiveness and V1 with the rate of 2nd phase slope (P < 0.001). V1 also correlated significantly with a calculation of infected cell loss (delta), which is a major determinant of the second phase viral decline. These results suggest that early viral kinetics may predict lack of response after only 24 h of treatment initiation and indicate a strong link between the degree of viral load reduction during the first phase, and the subsequent 2nd phase decline slope. This might be explained by a viral dynamics model assuming a jump-start of the immune response when viral loads are reduced below a threshold, subsequently giving rise to a faster 2nd phase decline slope."
http://www3.interscience.wiley.com/journal/118961281/abstract?CRETRY=1&SRETRY=0

"Patients who become HCV-RNA negative after 4 weeks have the best chance of achieving an SVR. The rapidity of viral elimination may be a useful guide to tailoring the length of treatment in patients with an EVR"
http://jac.oxfordjournals.org/cgi/content/full/53/1/15

And if you want to go in deep
http://www.medigraphic.com/pdfs/hepato/ah-2002/ah022b.pdf

[jmjm530]

Getter: Back to your original question, No it is not.
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Oh, almost forgot what the original question was, so I went back and read it. LOL. Respectfully, I disagree with your answer, because "<15" is UND and sensitive enough to be part of a decision whether to treat for 24 versus 48. weeks. I haven't read anywhere where "daily" or "weekly" tests are necessary -- or referenced in shorter course studies --  although some of us have had weekly tests. As to 72 weeks, that course only makes sense if you are detectible at week 12 which Jankar clearly is not.

In general, if you have a low pre-treatment viral load and are UND at week 4, there are studies that suggest that 24 weeks is a viable treatment option. Especially if you do not have significant liver damage. Jankar's original question below:

I had a result of UND<15 at week 4, someone else a UND<10 at week 4.  Is this result sensitive enough to base a decision on 24 weeks or 48 weeks?  Another suggested we needed weekly or daily tests in the first four weeks to make a decision, another suggested that those results are still detectable and if present at week 12 in the same levels, needs to result in 72 weeks treatment.

[geterdone]

Smart move! Just do it and be done with it.

jasper

[epiphiny]

According to latest journal entry jankar has decided to go the 48.

[geterdone]

Back to your original question, No it is not. At <15 there still may be thousands of virions floating around and many more in the tissues of the body. The best course of action is to do the SOC and that is 48 weeks. I was not in a trial and was never that lucky in Vegas to be a part of someone else opinion based on research of others and to be willing enough to take a chance in wasting my time that I have invested in treatment to cut it shorter than the prescribed time for the best chance of clearance. Everyone on this thread and most of the others here on med help did what? Went the full course of treatment and some then some. There has been a lot of good info put forth here but are you willing to be the genie pig and who will be there to hold you hand when they tell you the bad news? The www is great, but very unfeeling, so I’ll stick with my original post above.

jasper

[Bill1954]

Hi Zazza,

While I don’t have any published data to support this, I believe that while bDNA methodology is less sensitive than PCR or TMA technology, it is more *specific*. I treat with what is considered to be a cutting-edge clinic on the west coast, and they use both bDNA *and* TMA testing, both at the same time, for different reasons. If one isn’t looking for a highly sensitive test, I think bDNA is a very good choice; less chance of false negative/superior predictive value.

Bill

[merryBe]

http://www.medhelp.org/posts/show/383166

[merryBe]

it may seem everyone is speaking greek sometimes, but I know you are in new zealand, and may not have access to many of these tests. The debate has always been is UND really UND and of course that varies according to how accurate the test is, and how clean the machine is kept by the lab tech as well.

If you have access to more accurate testing you could ask your doc for a lab order to do the test there. Otherwise your options are to stick with the coverage you have or go out of pocket which can cost 700 or more depending.

the question is, if you are so close to UNDetectable that you will continue treatment even if a more sensitive test shows you still have 3 virons pr. mil.

the answer is yes of course you would still treat, your blood level reflects the virons being killed everywhere, in the liver especially as less are being released to circulate in the blood. Going UND early can make docs and people want to cut short tx but the newer studies all indicate that is a dangerous call as those treating longest after going UND all faired signifigant gains in their overall percentiles when it came to SVR rates.

I'll send you an interesting thread about test differences, but remember that early in treatment having the most sensitive test now would change nothing in your treatment guidelines. You will still treat for the prescribed time at minimum whether the test was a >50 sensitivity or a >1 sensitivity.

mb

[jmjm530]

The bDNA I'm familiar with -- and took -- in the U.S.A. had a sensitivity of 615 IU/ml. My understanding is that in '05 they using a test with a sensitivity of 50 IU/ml in your country.

[zazza]

So you're saying the bDNA only goes down to 615 IU/ml then? Interesting. Not long ago in that case since the testing was something entirely different than today. But would we in that case have gone directly from 615 to 15 IU/ml here in Sweden?

[jmjm530]

Like many, I also had a Bdna pre-treatment. As far as I know, it's a perfectly good test to use pre-treatment with someone having a HCV history because it would be highly unusual for someone pre-treatment to have less than 615 IU/ml. No Starbucks? What do you Swede's do with all the money you save on Latte's?

Getter,

Just get your doc to write your rx (with dx code of course) as follows and then take it to a Quest Center.  "HCV RNA QUAL TMA".

It's sensitive down to 5 IU/ml and an excellent test to take once you have become UND. In any event, it's good enough for me (and my docs) and it's the one I use.

-- Jim