Confusion about UND

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

[Deb_c430]

UND means undetecatable! They do differ in timing, but und is und!

[Proactive]

jankar, it appears you are undetectable to the extent of the test, which tests down to 15 iu/ml...congrats!!!
It was me who suggested the multiple tests, but as I stated, it really isn't practicle, and was more of a hypothetical statement on my part, sorry for the confusion.
I believe Zazza posted information pertinant toany shortening of tx decision..

[geterdone]

A geterdone moment here, at twelve and thinking 24, yeah buddyet! Danced around that fire then too. Slap, Slap. Ok, not big on gold digging here but Und at 4 weeks and being a 1b with a 244k and no damage pushing 24. I would get a Labcorp or hepamx pcr that goes down to <2 the next PCR and go from there and if you want the “insurance” split the last 24 and push for the 36 week middle ground and if you make it that far what the hell what's 12 more weeks at that point. Either way you’re going to… get er done!

jasper  

[epiphiny]

Can't get lower sensitivity test than "less than" 15IU/mL in NZ.  Considered trying to push to get my blood exported for more sensitive test but it seemed very tricky given blood is classed as a biohazard.

Wow, going for 24 weeks only sure is tempting given what you are trying to juggle. I notice you do have the low VL pre tx BUT only one of those so it's not a confirmed low VL as per the guidelines published in the other thread.

I know you want research and facts, rather than opinions but I gotta say shortening to 24 seems to be a pretty big gamble in my mind.  I can honestly say things got easier after the first 24 weeks and with a reduced stress/workload 48 might be more doable than you think at present.

Like jasper says, the most important thing is to get er done, and dusted!  Ex-nay the vi-ray!!  No coming back again....

[comeagain]

In sweden we use taqmantest <15 iuml or in log <1.18 what I have heard is that this test its sensetive enough and getting a more sensetive is just overdo it I guess there are exceptions when its motivated.

Whether you shall shorten your tx or not could be a good question to dr D if hes still answering any questions, or maybe you can consult another skilled hepatologist and ask what he, she, they think.

Anyway congrats to the very good result!!

ca

[Kristina538]

I got the same result at week 4 but am a G3.  

I was HUGELY disappointed not to be given a 12 week PCR which would have made me feel more confidant that the <15 coming in 'twice' was more significant of an UND result.    I questioned the same and my nurse said it was "as good as it gets" so I agree with Epiphany, that it's our lowest sensitivity test.

I would push hard to get more PCR's done during tx.   At least then, if you have to reduce your riba or peg during tx,  you will be able to make more informed decision on how it will affect your outcome.   A lady I know was on a trial (G1) and got the same result at 4 weeks but continued for the 48 weeks (she's 12 weeks post and recovering well).   Another lady (G1) is doing 48 weeks despite still being detectable at week 12.  Unfortunately the 48 weeks does seem pretty standard here for G1's and I'm wondering if your specialist has advised you of a possible cut down to 24 weeks (it would not be like NZ to be a forerunner - but thus far it seems you've had better treatment than in Auckland for testing etc!!)

However, weekly does get easier and I know that weeks 10, 12 and 16 were turning points in improvements on some levels for me, including my confidence levels on how my body was reacting to the meds.   Good luck Jankar and congrats on getting such an awesome result by week 4!!!

[copyman]

i think you can safely rely on that test that goes down to 15. The chances of having a VL under that number would be really unusal. I would get the more sensitive "qualative" test 4 , 12 & 24 weeks after stopping tx, this will simply tell you if you have HCV or not, no VL. I agree with the other posters that you look like the perfect cadidate to tx only 24 weeks and spare your body an extra 24 weeks of these harsh drugs. Like I have posted before I believe the permanent damage from these drugs come in the 2nd half of tx. The longer you subject your body to them the better chance of permanent damage. Best of luck

[zazza]

I had a detectable but not quantifiable reading at week 12 with the Taqman <15 IU/ml. The laboratory doctor told me this meant I had somewhere between 5 and 20 IU/ml. This sounds to me that in reality even virus below the stated sensitivity can get detected. Anyway my doctors tell me that it does not matter if we use <15, <10 or <2. They are equally good. Anybody ever here of anyone having a viral load of 4 or 7 IU/ml, for example? They just don't come that low.

[jmjm530]

I may be reading it wrong -- and perhaps your Taqman test does indicate positives below the quantifiable limit of 15 IU/ml.

That said, in general a test will not detect below it's stated sensitivity. For example, if a test states it's sensitivity as 10 IU/ml, it will not pick up a viral load of 5 IU/ml. It won't quantify it and it won't even mention it. Heptimax, for example has a lower limit of 5 IU/ml. It will not quantify or qualify below that limit. As to tests picking up a "4" or a "7", this is possible with a test like LabCorp's Quantasure which goes down to 2 IU/ml. I don't think it will quantify that low but it will qualitate similar I imagine to what your doc said, except that the lower limit of the range is 2 instead of 5.

[jmjm530]

To clarify, I'm not  contradicting your doctor and have no reason to believe that is how your result should be interpreted for your particular test.  My point(s) are that most tests do not work like this in terms of lower limit sensitivity as I read your inference, although I may have read it wrong.  The way they work is that if the lower sensitivity of the test is "x" then any virons present below "x" will still give an UND result, i.e. nothing will be picked up below the detection limit whether that limit be in a quant or qual test.

-- Jim

[Deb_c430]

Sometimes when you a person is having a  quandry about something, you find the answer, Thanks!  

[zazza]

You are reading me correctly. And this doctor is a very knowlegeable hepatitis specialist. I am certain he knows what he talks about.

I have not read up on this myself, but I figure that it might be that they can not guarantee they will pick up viral loads below 15 IU/ml, so they set the limit there. I understand it to be that so low viral loads as 5 and 15 IU/ml do not differ so much in test appareance, so it actually becomes difficult to tell them apart. And I don't think it matters what test you use.

[orleans]

UND at<15 is considered UND indeed(except for the rarest of cases} If you could get the <2 test that would be great (publicly funded health care does have it's own set of costs) My point is that <15 is widly accepted as sensitive enough. jerry ps Proactive was right in clarifying his first remark as wishful. Read the studies you can find on this subject. If you are married and / or have very involved friends have them help you wade thru them.     "The truth is out there" the X files!

[jmjm530]

Without knowing what version Taqman you took (for example there have been three versions in the U.S. within the last 18 months) and if it was pared with other tests, it's really difficult to ascertain exactly what your doc (or lab) guy had in mind when they suggested they picked up a viral load below the sensitivity of the test. And once again, I'm not contradicting or challenging your medical team, just furthering a discussion you opened up for both my understanding and that of the discussion group.  If you have your own hard copies of results including the exact test(s)/versions given it would be useful. If not, so be it. But again, in general, tests by their very description do not pick up virons below their detection limit and that's why they list a detection limit. That said, some tests can pick up virons below their quantifiable limit, but they still have a stated detection limit.

-- Jim

[Proactive]

Actually, it appears the tests can detect the virus well below their stated limits, just not 100% of the time...some down to very low single digit iu/ml numbers.
"The ASR detected 100% of the replicates containing greater than or equal to 40 IU/ml and 73% of the replicates containing the lowest concentration tested, 4 IU/ml. "

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=497598

[kciav]

I am confused on this also.

Directly from our lab report from Mayo Clinic at 4 week test the report states:

"HCV RNA detected, but less than 10 IU/mL (1.00 log IU/mL)
This assay cannot determine an accurate titer below this level.
Dynamic range of this assay is 10 IU/mL to 50,000,000 IU/mL (1.0 to 7.70 log IU/mL).
Testing was done by PCR method using the TaqMan HCV analyte-specific reagents.
Analyte Specific Reagent
This test was developed and its performance characteristics determined by Laboratory Medicine and Pathology, Mayo Clinic, Rochester MN. "

It looks like it is not UND yet but since the HCV RNA is detected or will it always show this?

[Proactive]

My opinion is, virus was still detectable below 10 iu/ml, but the test can't make that detection below 10 iu/ml 100% of the time. It can only detect 100% of the time down to 10 iu/ml. But verify with the lab--call the number on the lab slip where it was preformed.

[Proactive]

this was the same test given me throughout treatment, also sent to Rochester...call there

[Proactive]

Here is how one of mine reads
"HCV RNA Detect/Quant results: negative iu/ml
HCV RNA not detected"

so, the bottom line, you are within a knat's *** and are most likely undy as we speak!!

[kciav]

Thanks, that is what we are hoping for at the upcoming 12 week test, actually will be 13 weeks .  Wish they would do a test between weeks 4 & 12.
Congratulations on your test results!!

[Proactive]

Your son's journey is looking great so far!!! I was fortunate and did get tests monthly and then some, throughout treatment. I still was hanging on to 52,000 at wk 4, a bit over 2000 at wk 8...and unfortunately, 254 at wk 13...I had to take the long boat to China, but in the end, claimed my svr.
I wish your son the best,
Pro

[zazza]

My 12 week test (translated from Swedish):

Examination and test type:
DETECTION OF VIRUS RNA
EDTA-plasma

HCV RNA (Taqman)       BORDERLINE VALUE
(Measuring range 15 IU/ml - 69 million IU/ml)
Repeatable borderline value

General message from the laboratory:
With real time PCR for hepatitis C the earlier high sensitivity for qualitative PCR is combined with a large, quantifiable measuring range. In the same analysis is seen whether hepatitis C infection is ongoing or not, and if it is ongoing, current viral load expressed in International Units (IU/mL). Method comparison with earlier bDNA technique shows good linearity but that Roche new technique gives 0.5 log units (3 times) higher values in IU/mL.

[zazza]

My 15 week test:

HCV RNA (Taqman)      UNDETECTED
(Measuring range 15 IU/ml - 69 million IU/ml)

[jmjm530]

The results clearly state that HCV is detected, just below 10 IU/ml where it appears the test cannot quantify. No, the results will not always show this, assuming you get UND. In that case it will say "HCV Not Detected" or something like that.

Unfortunate that so many of  these tests are presented by the labs in such a confusing manner that even docs and NP's can't read them half the time.

One of the things I like about Quest's "HCV  TMA QUAL TMA" -- other than the fact that it can detect down to 5 IU/ml -- is that the results are reported simply in one of two ways. The results either say "Virus Not Detected" or "Virus Detected". Even a doc or NP can understand that!

-- Jim

[jmjm530]

Test mentioned should have been written: Quest's "HCV RNA Qualitative TMA" which is abbreviated as "HCV RNA QUAL TMA".

BTW this is an excellent test to take after becoming UND via a quantiative (like Heptimax). I used it  both at EOT and post treatment.            

[jmjm530]

It sounds like your 12 week test combined a quant and a qual therefore what your doc told you. The quant has a dynamic range of 15 IU/ml to 69 million. You would think they would list the sensitivity of the qual. I say "it sounds like" because things are never as evident as they should be with these test reports. I spent close to 20 minutes on the phone with the head of a major U.S. lab trying to find out some test specifics and left with the uneasy feeling that if I spoke to the head of one of the other labs I might get a different take :) Forget about getting a straight answer from "customer service" !

[Trinity4]

Doc in Atlanta recommend Labcorp HCV PCR TMA <10.  That is what he told me to have ordered.  That's what he uses.  

[zazza]

"With real time PCR for hepatitis C the earlier high sensitivity for qualitative PCR is combined with a large, quantifiable measuring range.In the same analysis is seen whether hepatitis C infection is ongoing or not, and if it is ongoing, current viral load expressed in International Units (IU/mL)."

It is ONE test which gives TWO readings, one qualitative and one quantative. So the measuring range is the same: 15 IU/ml - 69 million, for both the qualitative and the quantative. But with low enough viral loads it is impossible to determine what the quantative reading is, so there of the floating reading "5-20 IU/ml".

I have told you this before, Jim, simplified it is like if virus for example is determined by color or no color to show whether it is detectable or not. Then the actual shade of the color tells the quantative reading of the viral load. Thus you can get two answers from one test.

[zazza]

But when the viral load becomes really low, like between 5 and 20 IU/ml, the shade of color hardly changes, so it becomes impossible to quantify the viral load. This is because the change of color is not linear. It is linear while the viral load is high, but not at low levels. You can see that the virus is there, but you can not quantify the viral load.

[zazza]

"Doc in Atlanta recommend Labcorp HCV PCR TMA <10.  That is what he told me to have ordered.  That's what he uses."

This is what dr Thomas Berg recommends as well. I highly respect both Pearlman and Berg, so since they say <10, that is good enough for me.

[jmjm530]

Zazza: It is ONE test which gives TWO readings, one qualitative and one quantative. So the measuring range is the same: 15 IU/ml - 69 million, for both the qualitative and the quantative. But with low enough viral loads it is impossible to determine what the quantative reading is, so there of the floating reading "5-20 IU/ml".

--------------------------------------------------
I understand that and in fact that is EXACTLY what I stated to you. I simply asked what the bottom reading was, and apparently it's 5 IU/ml if you are correct. You might want to carefully read my posts before you get upset and disagree when in fact there is no disagreement on this particular point.  BTW at least my intent was not to make a pi**ing match out of who has the better test and what doctor orders what tests. Simply commenting on a few points you extrapolated from your own test that don't necedssarily hold true for other tests.

[jmjm530]

If you're going to use LabCorp, the test that HR recommends is the NGI Quantasure, not the Quantasure Plus which I believe you are using. The difference seems small to me, but not to HR as he states here and even more so in other threads. Not sure what Berg uses or what is even available in Europe.

As of two years ago, the most sensitive tests avail in the European trials was 50 IU/ml while in the States we could go down to 2 IU/ml. At that time a well known European researcher answered an email question from me and stated that any test below 50 IU/ml was basically a waste of time and money since 50 was sensitive enough. Now apparently 10-15 is sensitive enough in Europe. My guess is that in another 5-10 years, even NGI's 2 IU/ml limit will not be sensitive enough for HCV treatments. The lower we can get the sensitivities of these tests the more confidence we can have when we see UND. HR goes into this in some length in other threads.

HR:
"...It has to say HCV  N G I  quantasure  LC#140639, NOT   "LabCorp's Hepatitis C (HCV) QuantaSure " that is the small but important difference, these two tests are entirely different, done 3000 miles apart.
Dont ask me why it was named so very similar.......
Or for the qual part only  the " HCV NGI ultraqual" LC#140609 can bve used, same sensitivity, same
process, same test, just the quant PCR on the front end is left out.

Using the LC# is very important to avoid mistakes. "

Full thread here: http://www.medhelp.org/posts/show/728513?post_id=post_3851262

[Trinity4]

Understand but I remain confident that <10 will suffice.  I've never really agonized over sensitivities of PCR's.  It's really not an issue because at some point, I'll know if I relapsed or not after EOT so just going to keep the old fingers crossed and hope for the best.  I can understand it may be more important while going through tx, but after EOT the bottom line is I did or I didn't.  Actually, I may follow Facta's way of thinking and wait six months, then get tested.
Trin

[zazza]

I am not upset. Don't know why you got that impression. And I am not trying to determine which test is best, since my belief is that it really does not matter which test you use as long as the sensitivity is at least 15 IU/ml. Actually the ones used in the Vertex trials with a sensitivity of 30 IU/ml are probably good enough as well. I just don't believe that you gain anything by ordering additional tests with even lower sensitivity if you already have a sensitive one given to you by your doctor.

"As of two years ago, the most sensitive tests avail in the European trials was 50 IU/ml"

In November 2006 I was participating in a EU trial which used the Taqman test I mentioned above with the sensitivity of 15 IU/ml, so obviously you have the wrong information here. These tests are by the way the only ones used in Sweden since 2006. Berg's recommendations of a sensitivity of 10 IU/ml are from 2006. I don't believe Europe is behind the US in this sense. Certain doctors and researchers may not be up-to-date, but that is the case everywhere.

[kciav]

Thanks!
We will be looking for the Not Detected next test.

[jmjm530]

Trinity,

The principle that there are advantages to using the most sensitive test does not mean you should be confident in using a test with a limit of 10 IU/ml, which is quite sensitive. I use test(s) with a lower limit of 5 while LabCorp offers an lower limit of 2.

Zazza

Well, at least in the U.S., capital letters suggest "shouting" if not emphasis and the way you used them at a minimum suggested I was not listening to what you said, while in fact we had the same position. As far as the "2 years", yeah, time flies when you're having "fun" LOL. I finished tx 2 years ago but *started* tx 3 1.2 years ago in 2005. That was when I corresponded with the researcher in Europe where the most sensitive tests then were 50 IU/ml, according to the researcher. But at the same time -- 2005 -- I was using a test that went down to 5 IU/ml and LabCorp I believe had their NGI Quantasure (not sure on that) which went down to 2 IU./ml. I believe we also had Starbucks in this country several years before Europe :)

In summary, everything I've read and heard suggests using the most sensitive test available without going through too many hoops. I prefer Quest Labs to LabCorp so I'm not going through a hoop to get from 5 to 2 IU/ml. If I was in a trial that used a test with a sensitivity of 10-15 IU/ml, I'd feel comfortable. And if I lived in a country where the tests only went down to 50 IU/ml, I'd also feel relatively comfortable although not as comfortable with some UNDs as with a more sensitive test. My consulting hepatologist remarked at one point -- the discussion was extension or not -- that not only was I UND for "x" weeks, but UND down to 5 IU/ml. Obviously the distiniction was important to him.


-- Jim

[jmjm530]

prev post should read in part...

The principle that there are advantages to using the most sensitive test does not mean you *shouldn't* be confident..

[zazza]

Oops, didn't mean to shout, just emphasize. You probably are correct in that we mean the same thing, it is not always easy to determine, but it gives a reason to keep the discussion going. :)

My test from 2005 says this, no measuring range mentioned, so I wouldn't be surprised if it did not go below 50 IU/ml:

Examination and test type:
DETECTION OF VIRUS RNA
EDTA-plasma

1. Hepatitis C virus RNA   DETECTED

2. HCV genotype:
Type 1a detected

3. HCV RNA Quantative: 600,000 virus copies/ml
Test examined with bDNA version technique.

4. HCV RNA Quantative: 120,000 IU/ml
Test examined with bDNA version 3 technique, expressed as IU/ml.


I understand this bDNA technique is not used anymore. It is out of date now. Correct? Still without me knowing it, it was this old test result they used as my baseline. I was kind of upset when I understood they had used a one and a half year old test result for that.

[zazza]

We still do not have Starbucks in Sweden!

[geterdone]

I am going for another pre-surgery physical next week for the cataracts in the left eye and along with the std blood work and lipid test I will push for the pcr as well. My previous three pcr test have been Lab corps HCV N G I quanta sure LC#140639 down to <2 but my insurance will no longer pay for these test because Quest is the preferred provider. I know we have had this discussion before and you have favored the Quest lab test over the Lab corps test in prior posts and as with the present, so my question is what would be comparable to the lab corps. test down to <2 in the Quest testing? Is there a quest test that goes down to <2 or should the quest down to <5 be good enough being post treatment 11 going by the original start date?

Thanks

jasper

[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

[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]

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.

[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

[merryBe]

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

[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

[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

[epiphiny]

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

[geterdone]

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

jasper

[jmjm530]

Getter: Back to your original question, No it is not.
--------------
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.

[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

[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

[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.

[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.

[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.

[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...

[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

[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

[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]

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?
------------------------
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

[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

[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.

[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]

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...