I am finishing treatment the end of this month. I have been trying to figure out how to manage blood tests, doctor visits and TMA tests. I have not had a blood test in 5 weeks and was thinking - I have an open script for CBCs every 6 weeks - about getting one next week (at week 46). Would I need another blood test when I am done - only 2 weeks past this? Do people get tested immediately upon finishing tx or do they wait for drugs to leave system? How long should you wait? Can you get regular blood drawn when the 6 week TMA is done?
I dont have a doctor visit until two weeks after I finish. When is the best time to see your doc - seems that seeing her right at the end is kind of waste of time. Should I get another test before I see her? How about the schedule for viral counts - 6 weeks, 12 weeks, 24 weeks one year. Seems like a lot of tests - do people get tested this often? As I write this, it seems like stupid questions but I am pretty fried actually and am having a hard time stumbling towards the end of this thing. Any ideas would be greatly appreciated. Thanks.
The purpose of the end of treatment (EOT) test is to differentiate a viral relapse (after treatment ends) from a viral breakthrough (before treatment ends). This can become important information if you ever decide to re-treat. It is especially important if: (1) you haven't had a viral load test in some time; and (2) The viral load tests you took previously did not have a TMA sensitivity of down to 5 IU/ml. A recent study showed that a significant per cent of people who "relapsed" after treatment were in actuality PCR negative but TMA positive during treatment. That means that they didn't relapse at all, but either had a viral breakthrough during treatment or never really became non-detectible during treatment. Again, important information to collect in the eventuality of treating again. Therefore my suggestion of a very sensitive week 48 TMA which will dispel any confusion in this regard.
first congratulations on getting to the end of that stetch of bad road.
one way to answer your question is what could you possibly do with the test results or with the Dr. visit ? This is a minority opinion, but I'd recommend getting a CBC now, another one in 6 months, and only getting an RNA test when you feel you've recovered from the meds and are ready to take action in case of relapse.
The earliest RNA test that has been documented to correlated with SVR is at <a href="http://hcvadvocate.org/news/reports/AASLD_2004/Posters_AASLD_2004.htm#A62">thrree months</a>, though obviously, evey hour you stay negative the more likely you are to stay negative. The only thing testing at EOT could tell you is that you never cleared/broke through.
A better use of money is an EOT CBC. Assuming your levels don't return to normal in 6 months you'll want to know how far off base they were at EOT.
This is when they open the doors and let you go...the main thing at this point is to stay as far away from Drs as you can and figure how to put your life back together.
Thanks for that link as I had been looking for that study for quite some time. Unless I read it wrong, the 3 month correlated 100% with the 6 month but the 1 month also correlated 98% which to me is very useful data. I wish they would be more specific as to when they started counting (more important in the one month) -- did they start counting after the last shot or after the last riba dose? Maybe it's in the complete text version.
I respect your "minority" opinion not to be text fixated and get on with your life until you feel strong enough to re-treat if that's what is called for.
However, I still think a very sensititive 48 week EOT TMA can give important info for a possible future treatment by differentiating not only between relapse and viral breakthrough, but by also raising the issue if indeed the virus was ever non-detectible -- in the event that less sensitve tests were used to determine the non-detectible status.
Other reasons for early testing may have to do with both practical and psychological issues. From a practical point of view I wanted to know ASAP if I relapsed in order to do some necessary financial planning in the event of a possible re-treatment. That's why I took my first post-tx TMA as early as week 3. Why the SVR specificity hadn't been established for a TMA negative, the specificity for a TMA positive would have been 100% for relapse.
Another reason is that in some folks, knowing one way or another poses less anxiety that not knowing. I include myself in this category.
your points above are definitely part of the standard tx testing protocol (most people do an EOT test) but I've never seen any discussion of re-treatment that cared whether you relapsed on day -1,0,1...365 post-tx. Have you ?
Let's say you relapsed one month post treatment but it was established you were non-detectible during treatment. One reasonable conclusion might be you needed to treat longer.
But let's say you had a viral breakthrough at week 9 during treatment. One reasonable conclusion might be you should have treated harder with more drugs or even a different Peg. Same if you used less sensitive tests to start with, which brings up the possiblity that you were never non-detectible.
Remember the study I believe Goofy first posted. A significant number of EOT PCR negatives were actually TMA positives. 100% of that group eventually relapsed.
I really believe the more information the better. And what cannot be used with our current knowledge, might be valuable as our knowledge and new drug base advances.
Get the most sensitive TMA possible at week 48 while you're still on the drugs for an EOT baseline. Tests like Quest's diagnostic's Heptimax go down to 5 IU/ml. Then get a second TMA five weeks after your last shot, assuming you take riba for a week after your last shot. If you're non-detectible at this junction, it generally means you have a 90% chance of SVR. The next test might be at 12 weeks. If you are still non-detectible, your chances of SVR start to approach 97-98%. Next test at 24 weeks, which is the technical definition of SVR. If you're still non-detectible the chances are around 99% you will always be. Next test at 12 months. If you're still non-detectible your odds of staying that way are close to 100%. Some people test beyond one year but not sure if it's necessary.
Regarding your CBC's, I'd take them whenever you think you need them but don't feel you have to take them at the same time you do the TMA. On the other hand, there's nothing wrong with taking them at the same time.
Regarding your doctor visit, two weeks post sounds like a good time and you can then review your week 48 TMA as well as any other blood tests. So thinking it over, why don't you have CBC's and whatever tests your doc orders -- maybe a thyroid panel, etc -- at the same time you do your 48 week TMA.
You might then schedule your next visit two weeks after your 5 week TMA, so you can review results with your doc. Again, you might do your other blood tests at the same time.
Of course, if you're not feeling well, you can always schedule things more often.
In my case I saw my doc 2 weeks post treatment and 8 weeks post treatment, but I also get my blood results faxed directly to me from the lab and correspond with my doc and NP via email between visits. I'll probably have my next visit a couple of weeks after my week 12 TMA.
amen on the end of tx tma test. i told my dr. i would pay for it myself to know. i would like to get one maybe a week BEFORE end of tx so if it shows a vl count i might consider extending tx. the more tests the better i thik on making informed decisions.
you have been a wealth of info. thanks
TMA testing is available at most major labs. Here are a couple of TMA tests from Quest Diagnostics which is nationwide.
1. Heptimax -- Heptimax is really a two part test. First they run a quantitative real-time PCR which goes down to 50 IU/ml. If you're negative here, then they automatically run a quantitative TMA with a sensitivity of 5 IU/ml. The nice thing about the Heptimax is that because it's quantitative you always get a number somewhere between 5 IU/ml and however high the test goes which I believe is well up in the millions.
2. HCV RNA Qualitative TMA -- This is a very sensitive TMA test that goes down to 9 IU/ml. Because it's qualitative (Heptimax is quantitative) you don't get a number. You either get "not detected" or "detected" as a result. If you get "not detected" that means you have no virus down to it's limit of 9 IU/ml. This test is more useful EOT when a number isn't as important as your non-detectible status. It could also be used during treatment *after* you become non-detectible with a quantitative TMA like Heptimax. Quest's HCV RNA Qualtitative TMA may have other names with different labs but it's manufactured by Bayer and sometimes known as the Bayer Versant Qualitative TMA.
Personally, I used Heptimax from week 3 of tx through week 6 post treatment. The last time I treated (6 week post) I added the HCV RNA Qualitative TMA to the mix as kind of a belt and suspenders approach , as some posters here suggested problems with Heptimax.
Both showed non-detectible to their respective limits. On reflection, I think both tests are fine depending on what you need.
Lastly, if you wanted, I believe you can have the HCV RNA Qualitative TMA reflexed to Quest's HCV RNA Quant Real Time PCR.
That means first the run the qual TMA. If negative the test ends because you're non-detectible. If positive, then they run the real-time PCR which has a sensitivity of 50 IU/ml and I believe an upper range into the millions. It's possible that the tma may be reflexed to another PCR test but I seem to remember it being reflexed to the real-time PCR. This is a reasonable test strategy if you have reason to believe you're non-detectible but still want a number in case you're actually detectible. You could also run both tests simultaneously but it might cost more, if insurance doesn't allow what you're doing.
sorry my last post crossed yours. Here's the journal publication of the three month rule. Going back to the discussion of serum tests vs tissue tests, there's a limit to how much of an infection you can determine from looking at serum alone. The accepted model for virus replication intrinsically places much of the virus in cell cytosol, where it's not accessible to a serum test, regardless of how sensitive. Using TMA tests to detect residual infection goes back to Sarrazin's introduction of TMA in 2002, but the converse doesn't hold : TMA undetectable doesn't imply the absence of cell infection.
Also, while there seems to be a hierarchy of tx failure (no 2-log drop, no 24-week clear, 1 month relapse, etc. ) I've never seen this referenced in any re-treatment studies. They don't seem to care why it didn't work : either your immune sys learned to do its job or it didn't...
That's a good point about early post-tx testing for emotional, financial or insurance reasons. In fact, whoever comes up with with the first non-rx, RNA detection home kit is going to do very well (I'd like a case of those please....).
Willing says: (It) goes back to Sarrazin's introduction of TMA in 2002, but the converse doesn't hold : TMA undetectable doesn't imply the absence of cell infection.
Maybe not, but TMA undetectable does correlate with the accepted definition of SVR, which correlates with a better chance of halting or even regressing liver damage. Back to the study Goofy posted -- a significant number of EOT PCR positives were TMA negative. 100% of that group relapsed. What this says to me is that the TMA negatives had a better chance to halt or regress their liver damage. Again, I agree with your above point, but I think it's a little of apples and oranges with apples being the established benefits of SVR and the oranges being whatever might be the result of occult or persistent virus. Maybe one day we will come up with a hybrid fruit that will tell a lot more but for today I'm happy eating my apple but I respect you and Double Dose for sucking on the orange from time to time.
I think you might have hit upon something with the RNA home detection kit. In fact, I have the technology to devise one right now but can only guarantee 50% accuracy. The plan is to advertise the kit for only a dollar a pop and then I'll mail people a dime. Heads they're clear, tails they're not :)
Depending on the test and lab, you may have to wait up to two weeks for results of the TMA. Therefore, if you want the results before you stop treating, you could take it at week 47 and then extend treatment to week 49 or until a negative TMA result was in hand -- or, you could take the TMA at week 46 which should give you enough time to know before week 48. All the best luck!
Study says: End-of-treatment and sustained response were achieved in 624 and 342 patients, respectively. For all treatments, relapse was most frequent at weeks 52 and 56 and became rare following week 60. Only six patients out of 348 patients (2%) became HCV RNA positive between weeks 60 and 72.
Unless I'm reading it wrong, this study seems to contradict the previous study you posted (3-month link) that stated a negative 4-week PCR correlated around 97% with SVR. The above seems to suggest that most relapses occur between 4 weeks post treatment ande 8 weeks post treatment. Everything I've heard/read, including a recent discussion with my hepatologist suggests most relapses occur within the first month of treatment, not between weeks 52 and 56 or do they really mean between 52-56. I think maybe the answer lies in the full-text article but I've already spent too much money today to order it up :)
you're right, I wasn't paying attention. The Zeuzem paper supports a 5-month, rather than a 3-month rule; I can post it on the tinyurl site if you want, but you've seen what happens to the formatting.
As far as I can tell the paper Goof posted, which I assume is <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16271794&query_hl=39&itool=pubmed_docsum">Gerotto, et al</a> makes the same point as the earlier Sarazzin paper: in some patients sensitive tests will detect serum RNA at EOT; these patients effectively never cleared. However my point about the converse not being true has nothing to do with occult, post-SVR infection. Many relapsers have posted that they were TMA undetectable from some point of their tx onwards (my first TMA-type test was at 24 weeks, and was undetectable). These are not cases of occult, post-SVR, infection, just garden-variety relapses.
Your home-detection kit sounds like a sure-fire win. With some good marketing, that 50% accuracy statistic can be sold as a major breakthrough!
Wow, it is great to turn you guys loose on a problem! Its like having the "House" team kick around some diagnostic issues. Seriously, thanks for your input, I think I will:
1. Take my blood test next week. Just to check anemia and enzymes. The were up a bit on last one.
2. Get my doc to schedule a TMA at end of treatment. Get CBC at same time.
3. Meet with her two weeks after this to assess results and options.
4. Get a 6 week TMA RNA combo to see if we got some more work to do.
5. Order a new script for Riba in case bird flu hits.
If results are bad, back to drawing board, kinda like Willings get clear and refreshed and jump back in later. Maybe a little peg maintenance in the interim. There is just as long a conversation about what to do if your on the wrong side of the 50/50 highway. Thanks again - really!
Yes, I believe the Gerotto study is the one Goofy posted and please post full-text on other site if convenient. I'm still a little confused as the Zeuzem paper suggests most will relapse between 4 and 8 weeks post treatment, while everything else I've heard/read, including the Guzman study you posted earlier suggests that most relapses occur before week 4 post treatment. Hopefully the full text of Zeuzem will clarify. And yes, 50% accuracy will be a breakthrough with the advice some of us get from our docs :)
Actually, House is currently on freeze frame on my TIVO as I write this. Listen all the best luck and just make sure you get a sensitive TMA down to around 5-10 IU/ml like Heptimax. Lately, some are posting that their docs or NP's are somewhat clueless regarding test ordering. That's hopefully the niche where Willing's and my home detection kit will fit in. Got a dollar? LOL
the Zeuzem article is <a href="http://hepcassoc.org/messbrd/index.php?showtopic=11636">here</a>, though of course the formatting's gone. As I read it, the two articles are in pretty good agreement. Both report similar relapse rates, 22% and 26%, and report most relapses in the first 4 weeks. Zeuzem is much larger, but is older and didn't include riba. From Zeuzem's Table 2, of the 147 relapsers in the 180 mic PEG branch, 62% had relapsed by week 4, 89% by week 8, and 98% by week 12. Maybe a tad below what your Dr said, but not enough to delay chillling that champagne ...
After looking over things again, the Zeuzem study doesn't necessarily contradict those that suggest a non-detectible 4 week post treatment TMA correlates 90% with SVR -- something that the Guzman study seems to support. (Actually Guzman seems to suggest that the week 4 post-tx PCR correlates more than 90% with SVR as they state a 98% specificity).
The confusion -- at least with me -- is what I consider misleading wording in the abstract which is one reason I get so frustrated with abstracts.
Zeuzem reads in part:
"For all treatments, relapse was most frequent at weeks 52 and 56 and became rare following week 60."
That suggested to me that there are a lot of relapses at week 56 (8 week post treatment). But a more careful reading reveals that they only tested at weeks 52, 56 and 60. And since relapses between weeks 56 and 60 are rare (3-6 months post tx) then the ONLY possible weeks for relapse are weeks 52 and 56. And I imagine their full data would reveal that the week 52 relapses far outweigh the week 56 relapses.
Those figures seem to make sense but that abstract was really badly worded. I only took a glance since I'm ready for bed but will sift through tomorrow. One thing that did stick out though is that they used a detection limit of only 50 IU/ml, which is the custom with European studies. This could account for some of the later relapsers as they may have been under the radar earlier. Thanks for taking the time to post the full-text.
Ah, just picked up the no riba thing you mentioned in Zeuzem. I think that then suggests dumping Zeuzem for Guzman. Guzman is much closer to my doc's estimate with a 98% specificity between the 1 and 3 month blood draws. Still a little to early for any cork popping.
TMA (transcription mediated amplification) is a more sensitive technology for detecting Hep C virus in the blood. Two tests that use TMA technology are Quest Diagnostic's Heptimax and Quest's
HCV RNA Qualitative TMA.
The former is a quantitative TMA giving results in numbers, the latter is Qualitative, simply stating you are either detectable or non-detectable. Heptimax has a sensitivity of 5 IU/ml and the Qualitative a sensitivity of around 9 IU/ml. These tests are often suggested over less sensitive tests, especially at EOT and post treatment and also during treatment if a less sensitive PCR test is being used and the patient shows negative. A recent study showed that many PCR negatives may really be TMA positives. In other words, the less sensitive tests simply don't pick up the virus all the time.
LOL. And that's the only one we should make. Head's=SVR.
I would never go through the Pegasys/Riba again so it makes no difference to me about the testing. I will do my time (24 weeks left) and that is that. If I stay clear I do if not I will probably be tested in 3 or 4 years post treatment and if it pops back up then new drugs will probably be available. Not going to spend my life worrying about doctor appointments and blood work. I'm going fishing with my grandson, car shows with my wife, vacations in hot places, cut my mom and dads grass, never miss one of the grand daughters ball games and never go to bed until 11:00. That's my short list:) Dale
I'm doing fairly well for week 7. Maybe this Procrit is starting to kick in. I've only had 2 shots of it so far and it could be my imagination , but thats ok too. You have 24 weeks left.. thats got to be a great feeling. It's also got to be a great feeling to have made the decision to never do this again. I've gone for the longest time with the conclusion to my tx "open" . That really sucks to have no end in site . It's easy to state how many weeks of tx we have left , but we all know in our minds that its a good possibility it wont be over at week 48.Unless we want it to be. I do.
Have a great day.
One of the ladies that works with my sister in law finished treatment three weeks ago and she says the lady is like her old self now and energy is great and her mind is clear and sound. A little good news! Dale
I had my EOT TMA done about two weeks prior to last INF shot. That gave me time to get the result and continue TX uninterupted if called for - including and emergency second opinion - though we would probably have halted tx anyway.
On about 4/10 I posted several studies that confirmed a significant number of PCR negative txers will show positive if tested by TMA. The posted studies compared <50 PCR to <5-10 TMA. Apparently there are more sensitive PCRs than used in the studies -- going down to 2-5 IU. It's not clear to me whether it's simply a matter of test sensitivity or whether TMA is an inherently superior amplification technology. If it's a sensitivity issue, it would follow that the 2-5 IU PCR would be the best choice over all.
To me, the most important time to use the most sensitive test would be at the point that negative is first established -- but using it all the way through post TX would obviously be best. I think TMA costs about 4-5 times what <50 PCR does.
I have had 5 PCRs so far. My first 2 were at 12 and 24 wks tx. Sensitivity was <615 and I was UND. The next 2 were at 36 and 48 wks with a test called Super Quant from the west coast Mayo Clinic and tested to <10 UND. My 12 wk post-tx test was also UND <10.
Should I make a fuss to my Dr for a TMA at this point in my post-tx? He is difficult to work with and claims he never heard of Heptimax I go for my 24 wk post-tx PCR in a little more then 3 wks.
Ina: you're right of course, though I seem to recall there may now be another lab with FDA approval. Also, I think some of the lab techniques described in the Pham review TN posted above may be on their way to commercial labs. Can I ask why you'd want to jump right back on the Ingergen ?
Goofy: as far as I know, there's no clinical significance to the nuts and bolts of the amplification chemistry used in PCR, vs bDNA, vs TMA. It comes down to their sensitivity/reliability statistics. TMA just happens to be the most common high-sensitivity technique in commercial labs at the present. The larger issue is that a serum-based VL test is always a rough indication of actual cell infection - otherwise undetectable would be the same as SVR. As you point out, it mostly comes down to $. If cost is a factor, the only time the extra sensitivity tells you something useful is at 12 weeks.
Jim: throwing away data because you don't like what it's telling you is never a good idea... But as I read it, Zeuzem and your Dr. are telling you close to the same thing. If you take their numbers, at EOT you're looking at 26% relapse odds averaged across all patients in the peg tx branch. However, by week 6 roughly 75% of the relapses have clicked in and you're left with with only 6.5% relapse odds. The absence of riba clearly affects Zeuzem's overall SVR rate, but I've never see data that associated it with lower relapse or slower/faster relapse.
Willing says: throwing away data because you don't like what it's telling you is never a good idea.
Agreed and also the inverse :) My late night math coincides with yours but the other study (sounds like "zeuzem" but isn't) had even better odds --98% if I remember correctly on the week 4. I threw away Zeuzem, not just because the name is confusing to pronounce, but because of no riba, and also the fact they were using a less sensitive test. And, yes, I was a bit pissed at Zeuzem for that confusing abstract which suggested a first glance that there was a high rate of relapses at week 56, if I remember correctly.
I do believe I've heard riba dosage is associated with relapse rates but can't put my finger on it. I believe the reasoning goes that peg gets the virus down and riba keeps it down through a mutation process.
I do disagree somewhat with the statment that "he only time the extra sensitivity tells you something useful is at 12 weeks" and hopefully I'm not taking it out of context.
If I had it to do all over again I would have started with a sensitive TMA at week 1 and thereafter. My week 2 PCR was non-detectible, however the sensitivity was only 600 IU/ml. It would have been useful to know if I was indeed non-detectible at that point for a number of reasons.
Then, as Goofy says, assuming you're currently using a less sensitive test -- as soon you "clear" the virus down to the test's limit, it's really imperative you test via TMA to see if you have a real negative or a false negative in the sense that the virus is still detectible with a more sensitive test. The study Goofy posted regarding a significant number of EOT PCR negs being TMA positives brings this home to me.
How many people are currently treating who think they are non-detectible because of a less sensitive PCR, but really still have the virus if they test by TMA According to Goofy just about ALL these folks will relapse because they never reached non-detectible. From a clinical point of view, if they knew their TMA detectible status earlier, the treating doctor could have become more agressive with the drugs or even changed the Peg to help faccilitate response.
Post treatment, it gets a little blurred because what is done is done and eventually you'll find out. But if your're in a test early mode like me -- and don't want surprises down the road -- why not use the most sensitive test available. That way, you'll catch the relapse at the earliest possible point. Especially important if you plan to re-treat asap on relapse and in my case just for more peace of mind.
what does your dr want you to do? it might match what you have decided to follow, but it is probably best to make sure you are both in agreement. I would ask him what the protocol is in his practice, and if I don't like it, suggest my preference.
Mine told me, PCR and CBC 4 wks post tx, same at 3mo post and 6 month. We had a 48 wk PCR but nothing until 4 wk post tx, even I did not finish tx at 48. My feeling was that as long as I was on meds, the bug would not show its face, anyway.
I really think you've got much more imortant things to attend to, jumping up and down on the sofa for example, but if you insist here it is <a href="http://hepcassoc.org/messbrd/index.php?s=f9372a48018eeeab79ce712ec4cfa861&showtopic=11631">again</a>. It contains all the text and data but no formatting. If you can get me an address, I'll mail the pdf.
jim: re "My week 2 PCR was non-detectible", I hadn't heard; this makes the whole discussion (even more) entirely academic, your relapse odds must be approaching those of winning the lottery...
If money's no object there's no reason to not have as many sensitive tests as one wants. However last time I checked the <5 tests were running at about $350. Once you start tx, all you can do is stop or extend. As a 1, side effects aside, you would only stop if you didn't meet one of the two well-established cutoffs (2-log by 12, undetect by 24). The only documented basis for extending past 48 is detectable VL at 12 (Berg) or at 4 (TeraVic). All four guidelines are based on data from low sensitivity tests. That's why I believe the only time a high-sensitivity test can actually contribute to a tx decision is if you come up between 1 and 50 at 12.
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