Unblinded VL results - any opinions?

[lab-rat]

FOr those of you who have been following us vx trial participants, I thought I would share my unblinded vl results and ask your opinions on whether I should be concerned.  As it turns out, I'm in the placebo arm, so my results aren't nearly as interesting as most of the others.  It seems I'm not really much of a labrat after all, just a regular patient treating w/ standard meds.  I've been fortunate that I haven't experienced any dose reductions or debilitating side effects. In fact I feel pretty normal, which is great; however it appears I didn't quite meet the hallmark of a rapid responder. While I'm thrilled to be currently UND,I didn't really make it by week 4. Here are the numbers:

PreTreatment:
June '06 8,000,000+ (off-study)
07/28/06 3,070,000 TaqMan-RUO-CL
08/05/06 6,400,000 TaqMan-Exp-RUO-CL

PostTreatment:
Day 1 3,830,000 TaqMan-RUO-CL
Day 4 17500 TaqMan-RUO-CL
Day 8 16900 TaqMan-RUO-CL
Day 15 5348 TaqMan-RUO-CL
Day 22 1280 TaqMan-RUO-CL
Day 29 318 TaqMan-RUO-CL
Day 57 29 TaqMan-RUO-CL
Day 71 <30 IU/mL TaqMan-Exp-RUO-CL
Day 85(preDose) 29 TaqMan-RUO-CL
Day 85(post) <30 IU/mL TaqMan-RUO-CL
Week 16 29 TaqMan-RUO-CL
Week 20 <30 IU/mL TaqMan-RUO-CL

I need to go back and re-read all of the posts regarding the significance of the 29.  But there it is!

[lab-rat]

Hey Jim...you are absolutely right - I do need to know the specifics and get more details from the Dr. regarding his opinion on my lab results.  I guess I just felt the urge to defend my favorite nurse on the planet!  If this were my regular GI's office I would be a much more disgruntled patient because I believe they are clueless (not the case w/ my trial doc and nurse).  Thanks!!!

[mremeet]

Yeah I've often thought about the unpatentable drug/herb situation that stymies big research in these areas. First off, I think there's plenty of money to be made off of unpatentable products, including herbs and supplements. All we have to do is take a look at the existing herb/supplement industry and the billions in revenue it generates every year. Vendors may not have exclusive profit rights, but profit they still do. And this money is made almost exclusively from unpatented products with largely unproven (and often dubious) health benefits. Imagine if a particular herb/supplement was determined to provide a distinct medical benefit, especially for a fairly widespread life threatening illness like HCV? They'd sell plenty of it, and the manufacturers that made the highest quality and purest extracts could command premium prices - especially if there was a reliable independent certification agency overseeing enforceable standards of quality.

My mom takes and benefits from Glucosamine Chondroitin  shark cartilage extract (I think that's what's in it?). From what I've heard there are pretty reliable studies suggesting it really does help those with joint problems. My mom swears by it, and says it's made all the difference in her arthritis. And she happily pays the premium for the best stuff (Osteo BiFlex I think).

So I'm sure plenty of money can be made, it just won't be exclusive profiting. But that shouldn't be an overwhelming obstacle because the often huge expenses associated with development/formulation/synthesis are largely avoided. This should greatly lessen the need for exorbitant margins.

Of course that brings us to testing, and that is an expense no single company is going to shoulder. I think the government should get involved, although the government has a way of screwing up just about everything. It would have to be done the right way. I think there should probably be something like a consortium between private companies and a government agency that evaluates what substances are the most promising. The government could underwrite or heavily subsidize the research. The private companies involved with the consortium might also contribute some portion to the research coffers. In return, they can partially influence what substances are tested and contribute to the test structuring (proportional to their contribution). The trials can otherwise be carried out as they are now with "normal" drugs. Not sure how liability would be handled, but the govt would probably have to shoulder some of the burden. Maybe put caps on lawsuits too.

Occasionally I see supplements that claim to have higher "bioavailablity" like my Maximum Milk Thistle. They claim they extract the active ingredient from milk thistle and then either combine it with some other substance or somehow modify it using process xyz. The end result is claimed to be much more bioavailable than raw milk thistle, and therefore much more effective. I don't really know if this is a gimmick or not, but if it's true it's a good selling point (assuming MT is effective for the effects of viral hepatitis in the first place).

Anyway, I don't know if these types of processes which change or markedly enhance the potency of an herb/supplement are patentable or not, but I'd suspect some of them are. If the government subsidized testing proposed above did demonstrate herb X was great for shrinking hemorroids 50%, and it was determined what the active ingredient was that caused the hemmy shrinkage - then that could be a starting point for company Y to develop a synthesized or pharmacologically enhanced version of it. If its effectiveness was superior to the competition, and it was via a patentable process, then the motivation would definitely be there for the development of medically effective natural substances.

Oh well, we can dream. Makes you wonder what could be found out about natural substances if we lived in a perfect world though. If unlimited research dollars were available and we really started looking into everything? I'd bet we'd all live to be 150. ;-)

[lab-rat]

jim: you said "I would find the above answer
*extremely* unsatisfactory, be it from a nurse or my doctor. What exactly does she mean it "happens all the time"?"
_________________________________________________

I didn't mean to sound so flip about my nurses answer - but I'll admit that I like a little denial with my hepc!  My vl numbers were only faxed to me a couple of days ago and I haven't really had the opportunity to speak to the Dr. about them (he's out of the country quite a lot).  She called me at work for a completely different reason and we had a brief chatty conversation - I was uncomfortable going into too many details with her over the phone at work.  She's very experienced in treating hepc and liver transplant patients, and they do many, many trials.  If she tells me that the 29 is nothing to get excited about then I prefer to trust her judgement because frankly, what would worrying or obsessing about it do for me?  I intend to continue the treatment (as is), because at the very least it's giving my liver a rest and it hasn't been that big a deal.  Some people may think I'm being stupid or naive, but like you said there are other things on my plate!  I prefer to focus on my up-coming trip to venice to surprise my husband for his big 5-0!  That just seems like a more worthwhile ambition right now. I'm just going on auto-pilot with the tx.  By the way - I really do appreciate your input.  You've been a very valuable source of information for me!  

[jmjm530]

Point well made about the billions the herb/supplement industry is making. But since they're making all that money without investing in scientific double-blind studies, why should they? And can they really, on an individual basis, afford to spend the megabucks for these trials? Until then -- and govt involvement seems the only route -- there will always be questions about what does and doesn't work, quality control, etc. More important, there could be a real cure out there right now but who can really trust what with so many claims? Discouraging and a point in case where captiatlism and govt regulations don't always equate for the public good.

Mre,

My rant wasn't directed to you at all, just to the whole process we go through, often very frustrating because of the patronizing and often ignorant attitude of some of our medical providers. It sounds like you not only have a good medical team but have confidence in their advice, and I concede not everyone wants the same degree of involvement in treatment and I'm probably a little off the chart here in terms of my involvement. So it does **** me off, glad it doesn't **** you off, but the important thing is you appear in good hands and are comfortable presently with the information provided.

All the best,

-- Jim

[jmjm530]

We're pretty much in agreement, except if I was detectible at week 24, I'd probably simply bail out unless I was a very advanced stage 3 or stage 4, and in that scenario, yes, I'd be open to Oxymatrine and anything else that seemed reasonable. Other than that, I share your cautious approach to something unproven, especially if treatment seems to be on course. The problem, as HR pointed out in another thread on another drug, is that unless a drug can be patented and therefore have a huge potential payday, who is going to pay for the trials? This is where the government should step in but where are they?

-- Jim

[mremeet]

I posted on the meaning of the "29" situation a few weeks back on the first thread we had on this subject. It does mean detectable somewhere between 10-29 IU/ml (confirmed from my doctor). So assuming lab-rat's 29 results are accurate, which they probably are due to their alternating frequency, then it seems fairly clear she has been carrying a very low VL for the last several weeks. Not much ambiguity there in my view. However, as previously discussed in this thread, there's ambiguity because of the high sensitivity of our tests (<10 IU/ml) compared to the "historical" sensitivity of the PCR's used for the original pegIFN/riba trials. Like I believe you suggested above, it's not entirely clear if a patient experiencing a very low "flickering" viral presence strongly predicts/suggests future treatment failure. It's quite possible that many of the original pegIFN/riba trial participants who consistently tested "UND" with a <615 IU/ml PCR, may actually have still been HCV+ at a low level below 615 IU/ml throughout much of their treatment - and yet still managed to SVR. And since most of what we now know statistically about SOC response rates is based on these old test results, we have to be careful to remember the differences between the 10 IU/ml test used now and the much less sensitive 615 IU/ml test used then. In other words, if many of the old test participants who scored UND with the old test (and later went on to SVR) were tested with a 10 IU/ml test, with almost near certainty a fair number of them would have been found to still have still been HCV+ throughout at least some of their treatment at levels below 615 IU/ml, but above 10 IU/ml.

On the other hand, if I was still testing positive with the most sensitive test available beyond 24 weeks, then I wouldn't be comfortable with that at all. In my opinion, I'd perceive that as a likely harbinger of impending failure, even when considering the context of the historical VL response data mentioned above.

As far as oxymatrine is concerned, like I said I know very little about it. And normally I'd play it conservative too when it comes to treatment, and would stick to what's proven. But if I were still getting "29's" beyond 24 weeks, I'd start to vigorously investigate it and if it appeared to have a reasonable chance of assisting, then I'd probably take it. From what I know, it has a very safe profile. And although I know some supplements/herbs are known to possibly interfere or negatively interact with certain drugs, in general I think this is relatively rare. Offhand I'd guess the oxymatrine would be pretty unlikely to negatively interact with the IFN/riba or lessen its effectiveness. And if there's a shred of truth to the Chinese studies, then it may very well put the zap on those 29'er holdouts (especially working in unison with IFN/riba). Again, I can't speak with any authority on it because like you I know little about it. But at least I know Kalio's nose hasn't fallen off yet from taking it (along with IFN/riba), nor has she become detectable or had any complications. Desperate times call for desperate measures. In my view oxymatrine might be a trump card that could yield suprising results in a situation similar to lab-rats.

[lab-rat]

mremeet - thanks a million for your response and for clarifying the information on oxymatrine.  As I said, I'll have to do further research on that subject. Coincidentally, my study nurse just called a little while ago and I asked her about the "29"'s that were popping up on my labs and she said don't worry about it, they happen all the time in some patients. Maybe she said that to make me feel better...but it worked, and now I intend not to worry about it!

[jmjm530]

lab: my study nurse just called a little while ago and I asked her about the "29"'s that were popping up on my labs and she said don't worry about it, they happen all the time in some patients.
---------------------------------------
I know you've got other stuff on your plate but I would find the above answer
*extremely* unsatisfactory, be it from a nurse or my doctor. What exactly does she mean it "happens all the time"? That statement means nothing to me other than either the nurse was patronizing you or is simply ignorant what is going on. Also, did you or Mre get clarification from your doctors like APK did, regarding the signficance of "29". My understanding is that it only means one thing -- that you are detectible somewhere between 10 and 30 IU/ml. From some of the posts I've read here, I'm beginning to think that some of the study staff are confused as to what it means. This to me is beyond the pale but then again not much surprises me anymore. If I were in the study group, personally I wouldn't rest until I knew exactly what it meant if it meant knocking on Bolger's door. Lack of clarity in a viral load test is totally unacceptable unless you resign yourself to literally be a guinea pig as opposed to a human being who is able to participate in their own treatment. Regarding Oxymatrine again, I still go back to "don't rock the boat" if things are working unless you are *very* sure what you're doing. Kalio is Kalio, not you, and she is also re-treating after what appeared to be either a true viral breakthrough or most probably a relapse. Your case is diffferent.

Be well,

-- Jim

[mremeet]

What jim told you about how it may be possible that the viral load may simply fluctuate at very low levels in some people who later go on to SVR may be true. I was speaking with my doctor about the significance of the "29's" (I had one too btw) and he basically said the same thing. He said that the original testing/trials for peg IFN with and without ribavirin several years ago were conducted with a test that only went down to <615 IU/ml. And since that was true, he said it's quite possible that many of the patients who were testing "UND" back then and later went on to SVR, could have actually had some form of low level viral presence below 615 IU/ml during much of their treatment while testing "UND". There's no way to know now of course, but it's important to remember the profound difference in sensitivity between our tests (that go down to 10 IU/ml) and the older much less sensitive tests which were used to build the statistical database that's commonly referenced today when discussing likelihood of SVR when "UND" - we have to remember that UND at <615 IU/ml and UND at <10 IU/ml ain't the same thing!

As far as oxymatrine is concerned, I'm certainly no expert on the subject. I've just read dribs and drabs here and there about it fairly recently. I don't want to speak for HR, but from what I've heard you should probably not take it as a monotherapy (unless you're SVR already and are taking it for anti-fibrotic effects). The maximal effect you might derive from oxymatrine would occur if you were taking it in conjuction with other antiviral drugs like IFN and riba as a triple combo therapy. Ideally, you'd want to take all of these drugs up front simultaneously to whack the virus with everything you've got all at once. This way the viral population would be collapsed as rapidly as possible, which thereby thwarts the virus' ability to breed mutants (which differ meaningfully from the parent virus) that might be capable of later resisting the effects of the various drugs (and reducing your chances for an SVR). The virus' most powerful mechanism for survival is its incredibly huge breeding stock (roughly a trillion copies in most people), combined with its short life cycle and relatively unstable genetic structure. If you can annihilate the vast majority of the breeding stock in a blitzkrieged assault right up front, then you close the window on that most powerful adaptive mechanism the virus has for surviving a multivariable drug and immune system onslaught. A rapid viral decline is definitely thought to be critical in avoiding drug resistance and maximizing chances of SVR.

Anyway, in your situation you're not at the beginning of treatment and are already UND (essentially). So it's just a little unclear to me how possibly beneficial it might be at this point. However, off the cuff if it truly does have effective antiviral properties, then I'd certainly think it could definitely lend a hand to the IFN/riba in putting the cooties down for good. Obviously your virus (what's left of it) is oxymatrine naive, so it should be sensitive to it. Plus the breeding stock has been brought down to a very low level, so I would think the production of adaptive mutants in response to oxymatrine would be very minimal, especially with IFN and ribavirin still on the job (and apparently working well).

If you're interested, I would investigate it further and discuss it with both HR and Kalio. Kalio was knee deep in treatment when she started taking it not too long ago. Last I heard she was saying she felt alot better after taking it and was doing well. Plus I haven't seen her here much lately, so maybe it's allowed her to become more active?? I'd definitely talk to her and learn more about it. I've been meaning to do the same too, although like I said I remain somewhat skeptical for the reasons previously cited.

You ask about what would constitute a viral breakthrough in the trial: I probed this issue with my study nurse prior to being unblinded, and basically she didn't know. But from what I gathered, you could experience a viral reappearance of some magnitude and still not be "unblinded" or discontinued. The breakthrough would have to reach some undetermined level in order for the treatment to be considered a failure (and so be discontinued). But now that you're unblinded, will the doctor consider another 29 a breakthrough? That depends on the doctor, but I don't think so (largely for the reasons cited above in reference to the old 615 IU/ml tests). I would think they'd want to continue you, and I'd probably want to continue as long as I was tolerating treatment well (like you are). But I'd seriously consider taking the oxymatrine though.

Also, here's a link to the cholesterol study and increased SVR rates in case you're interested in looking it over. Take care...

http://www.natap.org/2006/HCV/080806_02.htm

[lab-rat]

Tallahassee - Thanks for the warning!  Guess I won't take that extra pill without permission.  As for the oxymatrine, I may end up trying that myself if this doesn't work out.  Good luck to you, I hope it helps!

mremeet:  I just wanted to make a correction to my previous post to you.  Where I said "LDL - usually around 70-80" - I meant HDL....where I said "friend of mine w/acute hcv for years" I meant "chronic hcv"...Even though I'm not exactly sure how my liver is doing, I know that my brain is being fried!

[Tallahassee]

Lab: When I was in study with riba in 1995-96, I noticed the extra pills too. Since it is was obvious to me that my viral load does not decrease as other patient's viral loads, I started taking an extra pill of riba every day (of cause, I did not know at that time if I was in riba or placebo arm)....

Well, at the end of the study they requested to return all my extra pills ... Apparently, the study people gave us extra pills just in case... I had to confess to my study nurse that I was taking extra pills...

They did not remove me from the study... but I'm not sure if the study nurse actually reported me to the Dr. I think she felt sorry that I'm not responding well...

Oxymatrine: I started taking it too (from 1/12/07)... I don't know what to do but I'm hoping to increase my chance for SVR ... I guess I'm becoming desperate :)


NYgirl: Congratulations on completion of 72 weeks of treatment!! You inspired me to look for approval of treatment extension.  Thank you for your constant inspiration and support!!  I think, I hope that you will have SVR!!!!  Wishing you (and everybody on this forum) all the best!!

[jmjm530]

Boy, wish I had those cholesterol numbers -- just hope in your case it isn't associated with liver damage. Contacting HR or one of the Fibroscan study centers might be an excellent idea. I had a scan mid-treatment myself and it helped me to decide how long to treat.

Except for some lingering skin problems, most of my other sfx -- GERD, sinus, ear problems, infections, etc -- are either gone or close to. What does remain is a lot of fatigue and lack of initiative and drive. Because of that, and my high cholesterol and tri's post treatment, I decided to change my diet a few days ago, so will try more of a "zone" diet -- less carbs, more proteins. Maybe that will help as my doctor just admitted that Interferon can make the metabolic syndrome worse and that appears to be the case with me.

Be well and good luck with tx,

-- Jim

[jmjm530]

Forgot about that study thing. Maybe they can ease the protocol since you're in the placebo group.

-- Jim

[Tallahassee]

Jim, thank you for your response.

Regarding my cholesterol numbers:

A nurse from University told me that my cholesterol was very high and I need to check with a Doctor (~1993).  Typically, young people think that they will live forever ... so I did not pay any attention to her warning.  In 1995, for my baseline blood work for my employment.  I think it was ~270-280.  Interestingly, when a nurse in 1995 called me to say that I have a Hep. C and need to follow it up, my first question was "How is my cholesterol?" :)  I definitely did not hear anything about Hep. C, but I knew a little about Hep B and knew that it is not treatable ... so why worry about Hep. C.   Besides, I did not have any insurance, so no reason to go to Dr. :)

While studying our diet consisted mostly from eggs, sardines, cookies, ice cream, chips, and ... more eggs with cheese. I guess diet was horrible :)

Definitely, now I'm more aware of my food ... though I still love eggs, but try not to eat more than 2 per day ... try :)

Now pretreatment (2005) total cholesterol was 118, I believe that couple years earlier it was ~149, and a year or so earlier it was ~169.  While on treatment, it is barely 100... though a good part of cholesterol was around 60 (above recommended range).  I also trying to eat a lot of fried food, etc. but it does not affect my cholesterol... so I keep wondering if my liver is not cable of producing cholesterol anymore??

I'm on daily Infergen (15-18 mcg) with Riba (1000 mg, I weigh ~115 lbs on average) and two weekly Neupogen (300 mcg?) shots. I self prescribed to myself 1200 of Riba (after some dispute, they mistakenly sent me 3 months refill too earlier). Also, I have extra Infergen, and after being negative from week 12 through April 2006 (viral break though), I was taking ~24 mcg daily of Infergen... for ~3 weeks ... my platelets got very low (in low 30s) ... so I had to stop this practice.

BTW, my Dr. was very close to prescribe me Procrit, but I will increase my "eggs intake" ... and I don't know for sure if it helped... but my Hemo will increase to 10-11.  

I went for consult to Gainesville and Dr. N approved 1 year of treatment after becoming negative (after viral break through in April 2006), ... he gave me only ~10% chance for SRV ... he said that they did not have convincing studies for Infergen ... since like it is very typical for patients either have a breakthrough or relapse... the same thing I was told by a coordinator in Miami.

I was on & off on Infergen from ~2000... this is the only interferon (even at 3 times per week) that kept my viral load <10... but due to  WBC drop and without rescue drugs, my dose will be reduced to 7.5 mcg (from 15 mcg) and my viral load will be back immediately... so at this point I just was very happy for having liver enzymes in acceptable range.

Per your recommendation, I was considering to have a FibroScan at HR's office (and I still planning it), but not likely we will visit our California relatives this April ... so may be by October...

Thank you for taking your time & for your help!

How are you doing after the treatment? I hope all or most side effects from interferon disappeared by now!!

When I tried cheerfully to convince Dr. from Gainesville that I'm very lucky and don't have the side effects I hear from this forum... He looked in my eyes and slowly  commented..."but you feel very-very tired... very tired".  I confessed that yes, I stopped exercising a few months ago and now at work I try to spend all day at my desk... He is right ... my tiredness level right now is unbelievably high!

All the best to you and everybody on this forum!!

[lab-rat]

mremeet:  Hi, I hope you're doing well!  Thanks for all of your helpful information.  I keep thinking about the significance of the number 29, and one thing that I found to be interesting is that on my day 85 labs, my vl was 29 before I took my peg shot, then a couple of hours later (post-shot) it tested as <30 IU.  That leads me to believe that these aren't just false positives, and that Jim is correct when he states that this is just the way the virus behaves.  It's sort of discouraging, that the cooties keep coming back (like the hitcher).  I also need to re-examine all of the study information and consent forms that we signed. I believe it states that if a person is in the placebo group and has a viral breakthrough, they would most likely be dropped from the study and would be on their own.  So it will be interesting to see - if the dreaded 29 rears its ugly head again, will the doctor consider that to be viral breakthrough?  I'll just keep plugging along with tx (as long as they keep giving me the drugs) and try not to dwell on it.

Also could you please clarify your suggestion about the oxymatrine...would that be something taken in addition to SOC?  Or as plan B if I need to go off tx?  I'll have to do some research on that, I've never heard of it until now.  I know that milk thistle has been beneficial to some and a good friend of mine w/acute hcv for years cleared the virus on her own (but was coincidentally taking milk thistle).  I have to be careful what I say about her, lest I be accused of selling snake oil!  

I'm glad to hear your cholesterol theory, because mine has been considered to be borderline high - although lately its been hovering just over 200.  A lot of that is my LDL - usually around 70-80.  I do try to be healthy by exercising and eating fruits and vegetables, but believe me, I eat plenty of ice cream, pizza, wings, red meat, butter, cupcakes, cookies etc. etc.  A day doesn't go by without dessert so I should probably be watching my sugar! In fact I've often thought that there must be some correlation between sugar and cholesterol.  Anyhow I'll be happy to keep up the fat-laden diet!

Jim:  I've been thinking about your suggestion of increasing the riba.  I've been given enough meds that I could just take the extra pill myself, but I'm not sure if that would be ethical, considering I should be following study protocol.  But part of me doesn't really care about the study protocol, since I'm in the placebo group anyway, who cares? Maybe I'll mention it to the dr. and see what he thinks.  Thanks for the suggestion.

[jmjm530]

Tall: What about the other study indicating that statins help to "destroy" the virus... Potentially it may become another antiviral remedy... If receptors of LD cholesterol and Hep. C are shared (I also read this study) then the same theory (just in reverse) may justify use of statins for cholesterol reduction.
------------------------------
This part always confused me. If high LDL is positive then how come statins (which reduce LDL) can help the process. Not that I pretend to understand this but the answer may lie in your next statment.

Tall: Since people with advanced fibrosis NEVER have high cholesterol, high SVR rate for patients with baseline high cholesterol may simply indicate that there is no advanced fibrosis is present - naturally suggesting the higher SVR rate.
---------------------------------------------------------------
Very good point and this could account for why treating with statins don't hurt SVR by lowering cholesterol pre-treatment. More important it could put an end to pre-dosing Ben and Jerry's ice cream, darn, too good to be true, eh.

I personally in 1995 had very high cholesterol - I was 25 years old, very skinny with okay diet. I started study - treatment with INF & Riba by the end of 1995 (48 weeks treatment) - I was considered non-responder. At this time they did not have a guideline for 2 log drop by week 12. I probably had only 2log drop by 48 week of treatment (from 20 mil to ~200,000). Biopsy showed a very mild fibrosis (stage1, grade 1). I had 100% compliance, no drugs reduction, and no rescue drugs (I don't think I needed any, probably because of the young age and being very healthy).


Tall: if most of the statins may be potentially used as antivirals, then why high fat diet (or high cholesterol levels) may potentially increase SVR??

Again, the question is whether high cholesterol is an independent factor for SVR or whether it's just associated with cirrhosis which is a negative predictor of SVR. Curious, you mentioned that you initially had very high cholesterol and now it's very low. Could you give us the approx numbers and did you do something -- either diet or drugs -- to reduce your cholesterol. Can't believe it dropped dramatically going from stage 1 to stage 2 or an early stage 3. I know my cholesterol ceratinly didn't drop. BTW late stage 2 or even early stage 3 isn't all that bad relatively. Where exactly are you in the treatment process now?

All the best,

-- Jim

[Tallahassee]

What about the other study indicating that statins help to "destroy" the virus... Potentially it may become another antiviral remedy... If receptors of LD cholesterol and Hep. C are shared (I also read this study) then the same theory  (just in reverse) may justify use of statins for cholesterol reduction.

Since people with advanced fibrosis NEVER have high cholesterol, high SVR rate for patients with baseline high cholesterol may simply indicate that there is no advanced fibrosis is present - naturally suggesting the higher SVR rate.

I personally in 1995 had very high cholesterol - I was 25 years old, very skinny with okay diet.  I started study - treatment with INF & Riba by the end of 1995 (48 weeks treatment) - I was considered non-responder.  At this time they did not have a guideline for 2 log drop by week 12.  I probably had only 2log drop by 48 week of treatment (from 20 mil to ~200,000).  Biopsy showed a very mild fibrosis (stage1, grade 1).  I had 100% compliance, no drugs reduction, and no rescue drugs (I don't think I needed any, probably because of the young age and being very healthy).

At this time I was very happy that my liver enzymes were in normal range during this (and all others) treatments.

Unfortunately, I'm not one of the lucky people who reversed their fibrosis - by 2005 my fibrosis progressed to stage 2 (I think that may be beginning of stage 3 by description).  BTW, through all my life I only had a little champagne on New Years nights - at start it was a principal not to drink plus without being exposed to alcohol, I did not crave it at all... later I new too much from bio chemistry class ... after being diagnosed with Hep C, I stopped having occasional champagne.   The reason I'm describing this just to show that I did not have additional contributing factor... well, actually, I probably was exposed to a complete table of chemical elements by making all my studies and researches in the labs...

Fast forward, prior to starting my current treatment, I had VERY low total cholesterol .. though my "good" cholesterol was slightly above recommended range.

I guess my question is:

if most of the statins may be potentially used as antivirals, then why high fat diet (or high cholesterol levels) may potentially increase SVR??

Thanks to everyone for your impute!

[jmjm530]

Come to think of it maybe pre-dosing with Ben and Jerry's might help. If indeed LDL shares the same receptors with the virus, then I suppose even an artificially jacked up LDL might be of some benefit, giving the virus less of a foothold so to speak while it's getting plummeted by the drugs. I certainly wouldn't recommend this to anyone but maybe HR might comment on this approach if he's following. The big question is: do you pre-dose with Cherry Garcia or Chunky Monkey? Personally, I'd opt for Coffee Heath Bar Crunch. This is one trial I might want to sneak into, just opt out when they hand out the peg and riba :)

-- Jim

[jmjm530]

Viral load was 16,000 at week 1 and <650 at week 2, using a not so sensitive test. I had it reversed in my post above.

[jmjm530]

re fluctuating viral load --

A false positive is always a possiblity but another is the possiblity that this is just the way the virus behaves if you test it frequently enough. In other words, it just keeps getting knocked down, then coming up for air, then knocked down, etc, and hopefully stays down for good. If that is what is going on then the next viral load test is critical although I don't think you have anything to worry about.

Like those in the Vertex trials, I also was tested frequently for viral load -- every week in my case -- until I became non-detectible. It went something like this: week 1: <650 week 2: 16,000;
week 3: 40; week 4: 55; week 5: 100; and week 6; <5 (non-detectible). As you can imagine, I was sweating bullets between week 4 and 6, but it turned out OK. Although my doctor brought up the notion of false positives, I don't think so. My feeling is that this is the way the virus manifest itself in my case either as a natural course of events or perhaps because of having to go off riba for a week around week 2. In any event, I don't think enough folks have been tested weekly -- or even more often like with the Vertex trials -- to come to a conclusion on this up and down thing at very low levels.

re Cholesterol

LOL. Sounds like something I might have done with the Ben and Jerry's if I was in Mre's shoes, however, not only was I unaware of the study when I started treatment but my cholesterol was over 200 anyway, so no need. I also seriously wonder if artificially jacking up your cholesterol would benefit or not, as opposed to just having a naturally elevated total cholesterol or LDL. Should it work, then we could call it the B&N Therapy -- pre-dosing with Ben and Jerry's -- but I really don't think it would help. I'll also add that my understanding is that the studies were *pre* treatment and not during treatment. Like some, but unlike many, my cholesterol signficantly dropped once I began treatment, almost from week 1. It dropped from around 220 to as low as 130-140, regardless of the fact that my treatment diet was cholesterol laden. This drop in cholesterol then was a function of interferon, nothing to do with SVR in my case. From what I understand, the virus and LDL share the same receptor. So, you would think that my cholesterol would have gone up during treatment, but again, it didn't. A lot we still don't know, or at least I don't know.

re Oxymatrine

First, I know nothing about it other than what has been posted here. With no disrespect to anyone, I'm just leery of adding anything to SOC that hasn't either been trialed or that someone treating patients can't vouch for in terms of seeing a successful result. So far neither of those scenarios have been posted here. That said, I'm sure if I was still treating and worried about a slower response, I'd look into it. However, if I had an RVR or even EVR, I'd probably be reluctant to add anything to a mix that apparently was working. I had to cross this bridge myself half way into treatment with a biologic called Enbrel that was recommended for my psoriasis. Unlike other systemtics, Enbrel supposedly wasn't liver toxic and in fact one preliminary study suggested it might help SVR. Still, given my RVR, I was reluctant to add another immunosuppresive to the mix and didn't. I'm sure Oxymatrine works on a different mechanism, but again, if it ain't broke, don't fix it, and if treatment seems to be working, don't change things. At least that's how I approached things almost to the point of being superstitious near the end in terms of riba, diet and all sorts of things.

[nygirl7]

sAID: Anyway, just prior to starting treatment I started wolfing down Ben and Jerry's, pepperoni pizza, hamburgers, fried clams, french fries, donuts, buttery pancakes, whole milk, whatever!


Hey............you took my fab diet advice!  :)

Seriously I eat like that but I just have a little tiny bit of what I want - and I've stayed skinny and have perfect cholesterol.  I watch other people who suffer through salad after salad after cottage cheese disgustingness - and taking pill after pill for their problem.

I think honestly - all good things in MODERATION are just how it was meant to be.

(So...down with another pint of B&J, Cherry Garcia for me!)


hee hee hee (hey the only fun part about treatment was eating all the ice cream that I could!)

[mremeet]

I think jim summed up your results pretty well. Good to see you responded strongly at first, but then sorry to see the mixed and somewhat ambiguous results later on. Hard to say what the best course of action would be at this point. But since you say you're basically feeling fine, then like you said at the very least finish out the 48 weeks as long as you remain UND. Another thing is, is that I'm just a little skeptical of all the "29's" we've been seeing. A 29 means you were detectable with a value somewhere between 10 IU/ml and 30 IU/ml. PDS had one at her day 85 visit just like you did. But she was UND nearly all the way up to it and the entire time after it. In our doctor's view, she probably scored a false positive, which he says definitely happens from time to time. Plus when viewed within the context of her particular consistently UND responses both before and after suggests it may be a false positive. Especially when viewed in conjunction with the fact that a viral breakthrough is usually a distinct event that will cause a much larger viral load to be detected than something between 10-30 IU/ml.

Unfortunately in your case though, these 29's have flickered on and off all along during the latter part of your testing (leading up to today). If these "29" data points are accurate, it looks to me like you're consistently remaining infected at a low level varying between UND (<10 IU/ml) and 30 IU/ml. Since this appears to be the case (according to these alternating on and off 29's), this apparently consistent (so far anyway) low level viral presence should be able to be detected using the supersensitive LabCorp PCR test that goes down to 2 IU/ml. Myself and PDS both got this test to verify we were indeed negative. HR also recommended this test because it is processed at the top lab in the US, which is held to the very highest standards of accuracy/quality control. I would definitely schedule a series of at least 2 or 3 of these offstudy tests and have the blood drawn on the same day as your scheduled study visits. That way if another one of these damned 29's rears its ugly head, you'll have a definitive referee to resolve if these are legitimate positives or not. If one or more of the next 29(s) turns out to be bogus, then that should bolster your confidence that at least some of your previous 29's may have been false + too. If the 2 copy test vindicates the 29(s), then at least you'll truly know where you stand with your treatment.

Lastly, Kalio has fairly recently added a supplement to her regimen named Oxymatrine. Oxymatrine is a derivative of the sophora root, an herb used in traditional Chinese medicine (TCM). According to several Chinese studies, oxymatrine has been shown to very significantly lower HCV viral loads; even to UND levels in some people. It also supposedly has anti-fibrotic properties. Normally I'm very skeptical of such claims, especially when there are no corresponding western studies (that I know of) to help correlate the Chinese claims (yes, I'm a bit of a xenophobe when it comes to unvetted TCM claims). On the other hand, and I don't want to speak for HR or misrepresent what his stance on Oxymatrine is, but I have seen him express at least some optimism for this substance. He made no claims it would cure, nor did he  outright endorse it, but I believe he definitely believes it is a substance that is worth investigating further. And as you probably know, he's pretty uniquely qualified to provide a well informed opinion on such a thing. If the Oxymatrine truly does have antiviral properties, the possibility of adding oxymatrine to IFN/riba therapy could very well tip the balance and finish off those last "29'er" holdouts. And if it truly does possess antifibrotic properties, then obviously you'd also benefit from that as well.

Of course if you did decide to take oxymatrine, you'd probably have to discontinue from the study. Although you never know, they might let you take it - they might assume it would be ineffective as an antiviral agent. Also, apparently it has a very safe side effect profile, so that shouldn't pose a problem. But even if you did have to discontinue from the study in order to ("legally") take oxymatrine, if you know your virus is managing to consistently hang in there at low levels, then what do you have to lose? I'd definitely take it and see if it would help. Who knows, it might make all the difference. Talk to Kalio or HR to learn more if you're interested, also you can just google it and check it out for yourself.

Oh, and one more thing, and sorry to be so long winded. But I have been maintaining a high cholesterol level throughout my entire treatment. There was a compelling study published shortly before starting on this trial that strongly suggests that those that maintain high cholesterol, especially high LDL cholesterol (i.e. the "bad" type) are significantly more likely to achieve SVR than those with low cholesterol. And this study didn't just suggest some vague and statistically weak correlation between slightly higher SVR rates and high LDL cholesterol, it was fairly definitive. And the population sample size was a couple hundred people too, so it wasn't a study based on small numbers (which would statistically be much less meaningful). Plus this study was premised on previous studies that also suggested this same relationship between SVR rates and cholesterol. And they had an apparently logical and sensible theory explaining why high LDL cholesterol levels would help to interfere with viral activity during treatment.

Anyway, just prior to starting treatment I started wolfing down Ben and Jerry's, pepperoni pizza, hamburgers, fried clams, french fries, donuts, buttery pancakes, whole milk, whatever! And man I achieved my goal. At one point my cholesterol was 285, and I don't recall offhand what my LDL was, but it was quite high, I'm sure it was in the "I've fallen and I can't get up" zone (lol). And I've maintained my cholesterol above 225 pretty much the whole time, with the exception of my last test which showed 195 (I couldn't stand whole milk anymore, so I suspect my move to 2% accounted for the drop). I can't know exactly what role my elevated cholesterol might have played in my good response rate, but I often wonder if it made the difference for me. Especially during my time of crisis when I had stopped the VX, interrupted my riba and was taking prednisone all at the same time. I thought for sure I would of had a viral breakthrough during that troubled and vulnerable timeframe, but it didn't happen. Was it my disgustingly fat laden diet that saved me?? Who knows, but it might have.

I know you're a healthy and active person who exercises and takes care of yourself. I'm not advising you to ruin your diet because of the obvious negative consequences of a high cholesterol diet. But speaking for myself, I'm willing to take the risk temporarily with the thought that I'll clean up my act and return to skim milk and roasted skinless chicken after completing this treatment.

Keep us posted on your progress, take care.

[jmjm530]

Don't know your pre-tx hgb, but 12.9 is pretty decent on tx, therefore you might discuss with your doctor bumping it up to 1200 to give you a little more oomph since you were still detectible at week 12. Keep in mind some more side effects might follow but you could always drop back to 1000 or even go on epo if allowed. He'll probably tell you that extra riba doesn't help so late in the game but maybe he will be open if you bring up the fact you were still detectible at week 12 again.  I assume they will still test you monthly for viral load. If you do get "29" again -- and I doubt you will --  probably time to seriously reassess.

[lab-rat]

Thanks nygirl.  72 weeks must seem like a lifetime doesn't it?  I'm only on week 22 so it's hard for me to imagine that.  You must be done soon?  

I'm just going to keep plugging along and try not to check the calendar (LOL) and see what the monthly vl tests bring.