News Sstories and Other Posts

<a href="http://www.natap.org/2005/AASLD/aasld_38.htm">Albuferon-Alpha (Albumin-Interferon Alpha)</a>

<a href="http://www.natap.org/2005/AASLD/aasld_39.htm">Consensus Interferon: study results at AASLD</a>

<a href="http://www.hivandhepatitis.com/2005icr/aasld/docs/111805_c.html">Short-term Treatment Duration for HCV Genotypes 2 and 3 Patients</a>

<a href="http://www.hivandhepatitis.com/2005icr/aasld/docs/111805_b.html">Albuferon Plus Ribavirin in Nonresponders to Interferon Therapy</a>

<a href="http://www.hivandhepatitis.com/2005icr/aasld/docs/111805_a.html">Does Weight-based Ribavirin Dosing Increase Sustained Viral Response in Patients with Chronic Hepatitis C? Final Results of the WIN-R Study</a>

[TnHepGuy_]

<u>Kalio1</u> - It looks like they are concluding what is already known: that 24 weeks works just as well in terms of overall SVR figures as does 48 weeks in geno 2's and 3's. But that data pool includes all geno 2 and 3 patients and makes no distinction between those who have high histological damage, those who don't reach ERV goals, those who don't reach 12 week goals, previous non-responders and relapsers, etc. Those are generally the factors that are taken into consideration when deciding on whether to extend beyond 24 or not.

As far as the SVR figures presented here in this study, by their own account it is being published as being potentially seriously flawed due to the extremely high dropout rate of 37%. When they try and correct for that the composite (across all genotypes) SVR rate rises to 56% (12% higher) for WBD and 51% (10% higher) for FD - somewhat closer to figures seen in other studies.


<u>beamishboy</u> - the general consensus is that riba is most important over the first 12 - 20 weeks of tx for geno 1's. If you wanted to try and up your dose by 200 mg/day - run that past your doc, explain your reasoning (with study and paper documentation) and ask for more close monitoring of your CBC's along the way. Also, be sure that he/she would intervene proactively with Procrit before considering any dose reduction other than back to your riba starting point. And no matter if you up your dose or not, you want your caregivers to state flatly up front that they will rx you proactively Procrit and/or Neupogen, should either be needed.


TnHepGuy

[Wasabi Pea]

Regarding riba dosing, although I am of the thinking that the more you can keep in your system for a longer amount of time is better, I seem to suffer from acute anemia...so much so that I was reduced from 1200 to 1000 (due to weight loss), then 1000 to 800...to 600...to no riba at all for a month...back to 200 for a month...and now I've been on 400 for two.  I've been very concerned about these huge reductions....

However, the good news is my last PCR, which detects down to 10 copies, I believe, showed undetectable!!!!  Yay!  I still asked to be upped to 600, to see if I could keep my hgb in the 8's, but the doc wants to wait a little to see if procrit will move it up into the 9's or not.  

I guess that's why he's the doctor and I'm not. <g>  Very, very hard to be patient.  But I'm taking the good news for what it's worth and relishing it. <g>  Hopefully, I can stop tx between Feb and Apr.  

Wishing SVR for everyone!

[beamishboy]

thks 4 info..i am day4 on peginterferon&ribarivin-1200...i am 49 yr old male.type 1b w stage 2,3 biopsy results;i weigh 215 lbs(lost 50+ in the last 9 mo. in prep 4 trx) shud i consider uppin my dose of ribarivin? to 1400? i want every advantage i can get& 5% increased svr seems v significant to me....please comment-thks---hey the sun is shinin & we got just a bit of snow last nite-beeeutiful!!!!

[cuteus]

yes, I had read that one too and found it interesting, but I think the g3 did get some benefit? I have to go back and read it, it seems that some feel that g3 should not be grouped with twos anymore. So much too read!

[NYgirl]

Wasabi do they have you on Procrit of Epogen?  I dont remember if you mentionned that or not.  That is GREAT news about the PCR great great great!

Girl question - if guys are squeamish read no further:

Did anybody just start skipping their period altogether? I know I lost about ten pounds and only started at 125 (41 yo 5ft7in) so now I am pretty thin - shot 9/48 tonight...and I have that acute anemia thing going on (no hgbs running around?) but it's just like GONE and I am positive I am not pg (thank God I'd kill myself ;-) just too old for that now...had my tubes cut, tied and burned after almost dying with both my kids.  Plus I have no man so it would be HARD to explain right now hahaha).

I've heard of it being a MORE situation but not a NEVER situation.

(PS Don't want to call my doctors office to go in and tell him this and have him say "well everyone is different" or some drivel and waste the copay and time off work!)

[NYgirl]

Dont want any guys to get bugged - I thought I tagged it to Wasabi and Girl Question but I must have forgotten!

[cuteus]

that subject came up last year and yes, it seems to affect many women the same way. they also started up again after tx, so your monthly friend might return. I was on contraceptives so I saw no menses stopping at all. I am not sure if that would make a diference.

Kalio; I used to sit in front of my PC at work and stare blankly at the monitor for hours.  Someone posted she was in college while tx, I admire her completely. I could only remember my name and where I lived, and my girls.  But I went to six flags with them when on tx and did not remember the oldest one had been visiting during that time(she is out of state). Pretty scary.

[NYgirl]

Hey I have the worst brain fog and I am not even sure how much of it I can honestly blame on the tx ;-) but the depression is OK until something goes wrong then I get VERY upset (with myself a lot you are right).

For example my son was very sick the last two weeks and as a result didn't make the bball team like he always does. He was so upset and all I could do was sit in the car and SCREAM a big giant why me...where did I go wrong...life sucks speech to the sky! Crying, screaming, sobbing like a nutjob. Like it was something I did to him.

But otherwise the ADs seem to be doing their job on a day to day basis.  Are you on any? They really seem to be helping me.

Man I simply cannot BELIEVE you have to feel anemic and NOT haVe it be it so you can have a cure! I am absolutely just going to CRY over that. It was so horrible....so horrible I just don't know how you are managing like that!!!  My God I hope it goes away just like it came.  Don't they have ANY idea at all?!!!!!

Thanks girls (and dear old goofy too).  I used to like having my "friend" come to visit cause I knew I would lose a couple of pounds...but now that I've already lost so many in two months I guess I dont need to look forward to it for that reason anymore anyhow!

It just really freaks you out! Thank GOD I know the "baby brewing" equipment is long since been knocked out of order!!!!!!!

[TnHepGuy_]

(continued from below post)

cuteus - thanks for the kind words. Yeah, going into tx and early on I was preparing for the possibility of extended-tx due to HVL and previous failure going in. But the more that I thought about things (low degree of histology, HVL was "only" 2,400,000 - which I would classify as 'mid-level', not really being a 'true' non-responder since I had failed alpha-interferon - not peg and riba), coupled with being clear at Week #12, I decided that 48 was the goal for me. So far, so good.


Eisbein - thanks for the kind words. Great to hear you've got a doc like that who will go the extra mile for you. They can be a rare find. And it seems as if you've found the strategy that's best for you.


goofydad - since the "the various costs of tx" are almost completely unquantifed at this point in time, the category of 'costs' can then become a catch-all for all kinds of things - be they perceived or actual. Any valid econometric model (not that one would ever be proposed) would have to take all of the available data on the hepatic and non-hepatic manifestations of HCV (which tend to get the brush-off in these discussions since the easiest thing to focus on is histology as the 'big boggieman'. Even the long-term potential of HCC tends to get played down), add them up to come up with a "No-tx Risk Factor". Then add up all of the quantifiable risks of the meds during and after tx to come up with a "Tx Risk Factor". Then do a comparison. Would any of this (impossible to get) information help an individual make a better decision than they can today? Most likley. But it still would be rather limited by being generalized information applied to an individual situation. Once again the patient and doctor would still have to base their decision-making upon the factors that the individual brings to the table. Comparing them to group data certainly can be informative and helpful, but a patient makes

So what are we left with today? A patient can semi-accurately gauge their SVR chances via trials and extrapolations upon the individual factors they present. Along with that is available data on the potential improvements in histology via SVR, maintainence and tx itself. A large grey area is in bringing together all of the non-hepatic manifestation data together into a unified, simple-to-read, single publication (which would undoubtedly need constant updating). On the other side is a near vacuum of information related to tx and post-tx related issues and concerns. These, too, need study, quantification and publication. But I wouldn't look for much in the way of that anytime soon. The dollars tend to flow to tx, basic research, etc.


"is it possible that more over-txing is occuring than what is obvious to us?" - not only possible, it happens every day of the week. For example, I tx'ed for 48 weeks. I was clear at Week #12 (no earlier PCR's done - thanks to my mostly traditonal gastro). I may very have been an EVR (based upon guess work from my LFT's during that time). If so, it's quite possible that I could have finished tx'ing earlier. Undoubtedly, I didn't sweep the last of the little bug out of my liver on the 336th day of tx. Therefore, I am an "over-tx'er" - be it by one day, one week, one month, etc. Over-tx'ing is the norm in acheiving SVR. Under tx'ing is non-response, rebound or relapse - by definition. If there were a blood test available that could find the point of either complete viral elimination or the point at which chronic infection tips over to the occult stage (with no hope of full eradication, that is), tx timing could be narrowed down near perfectly. But no such test is in existance. So we over-tx (at least to some extent or another) in hopes of 'catching' the most SVR's. Have I paid a personal post-tx price for my "over tx'ing"? It's possible. My Hg hung around 11 after settling out. That is until the last 6 weeks of tx, when it eventually bottomed out at 9.8. At 7 month post-tx my Hg (and WBC) was still low (defined as within one point of starting baseline). Are the benefits gained from SVR worth it vs. anything lingering via tx? Not even close. I have done the absolute best thing available today to improve not only the health of my liver but anywhere else within me that the active virus attacks and destroys and/or diminishes function. I've improved my mental health by removing a specter that has hung over me since dx and initial tx failure in 1992. And not only are the benefits limited to me, but my wife no longer worries of her husband's potential to progress onto severe liver damage. Nor does she cry over all of the times that the Hep C itself took it's physical toll throughout the years on her mate. And friends and family have my burden lifted from them, as well. The 'benefits' list goes on-and-on.


TnHepGuy

[GoofyDad]

Ampersands (the 'and' sign on the keyboard) don't work in the 'To' field. Happens to me all the time.

Hey, I'm not bugged - I love this stuff. Reminds me of spying into the girls locker room in middle school. Oh the days!

[cougareyes]

I find that the maifestations of HCV and the possibility of HCC to be more overblown. I have not seen any information from legitimate sources as the Mayo, UCLA, or John Hopkins that say statistically that people with HCV have a greater chance developing any of these conditions. And the statistics of HCC are so very small, you have a much greater chance of dying any number of ways before you develope HCC. So much of this is simply scare tactics manufactured by the drug co. and the pro-tx doctors.      Peace

[TnHepGuy_]

<a href="http://precis.preciscentral.com/Files/Source/116/AbstractPDF/63984.pdf">Behaviour of sustained responders to anti-HCV treatment: may HCV infection be eradicated?</a>

(from the paper):

"<i>This study suggests that combined therapy may lead to viral
eradication in the majority of HCV+ pts. Even if it is impossible to exclude viral persistence at undetectable levels, it does not seem to have clinical relevance even in the case of OLT. Persistence of viral infection in uncultured PBMC was only observed in MC with clonal BL expansion. A tentative explanation may be related to the expanded life of t(14;18)+ BL. Although a different evolution of LPD may not be excluded,

[TnHepGuy_]

trying to figure out how riba does it's thing:

<a href="http://precis.preciscentral.com/Files/Source/116/AbstractPDF/65089.pdf">Assessment of ribavirin mutagenic properties in vivo and the influence of interferon
alpha-induced reduction of hepatitis C virus RNA load upon therapy</a>

(from the paper):

"<i>Ribavirin does not appear to be a mutagenic agent in vivo, either in monotherapy or in combination with IFN alpha. However, this property could be revealed when HCV replication is reduced to very low levels by IFN, a hypothesis currently under study (these results will be presented)</i>"

[TnHepGuy_]

<a href="http://precis.preciscentral.com/Files/Source/116/AbstractPDF/67446.pdf">Ribavirin plasma concentration is predictive of sustained virological response in HCV
infected patients. A prospective study</a>

(from the paper):

"<i>Patients with SVR had higher ribavirin plasma concentration at week 12 than non-responders. Three in four patients with a concentration higher than 3 mg/l at week 12 were SVR. Therefore, early determination during treatment of plasma ribavirin concentration (with a target concentration of 3 mg/l at week 12) could be useful for monitoring HCV therapy. The impact of ribavirin dosage optimization, to obtain such a
target concentration, on SVR rates should be further investigated.</i>"

[TnHepGuy_]

<a href="http://precis.preciscentral.com/Files/Source/116/AbstractPDF/61115.pdf">HEPATITIS C VIRUS PERSISTS AND REPLICATES IN THE LIVER OF THE MAJORITY OF SUSTAINED RESPONDER PATIENTS TO ANTIVIRAL TREATMENT</a>

(from the papaer):

"<i>HCV persists and replicates in the liver and PBMC of the majority of the patients with chronic hepatitis C after a sustained response to treatment, although they maintain HCV-specific cellular responses. As these responders have not cleared HCV infection and may maintain histological damage, they
should be followed for years in spite of apparently clinical resolution of the disease.</i>"

[jmjm530]

I have two papers that may be of interest somewhere on my hard drive in PDF format. I don't think they're on the net, and I'm unable to host them. If of interest, I'd be glad to email them to you and perhaps you can do your magic links and share them with the group.

Both papers are earlier studies by K. Lindahal and Group, the Sweedish researchers known for the recent high-dose riba study, which I also should have somewhere in its complete form.

Paper 1: Evidence that Plasma concentration rather than dose per kilogram body weight predicts ribavirin-induced anemia.

Paper 2: Dosage of Ribavirn in Patients with Hepatis C shoud b based on renal function. A population pharmacokinetic analysis.

-- Jim

[Chriskid]

Interesting on RVB plasma concentrations.  So where can I get tested in this country?

[DoubleDose]

The Carreno study that you posted above, regarding the prevalance of replicating HCV in liver samples, four years after SVR, is typical of recent research, and very DISTURBING!

Not only does this imply the possibility of re-activation of the virus by the right stimulus (immune system dysfunction?, over-consumption of alcohol? extreme physical/mental stress?, or other), but ALSO implies the possibility of ongoing low level damage through direct viral action, or chronic immune system regulation of the virus!  I wonder why THIS study (and a few others) finds the virus alive and well in almost all the SVR's, where several other studies of liver biopsy tissues have frequently shown the opposite result, even after much amplification????

This research study fits one of my 'occult' virus theories.  In a nutshell it goes like this:  There may be MANY people out there who harbor an occult form of the virus in their systems, but not the typical blood/liver infection.  They may have no obvious blood antibody markers on testing (neg. HCV antibody test), and may never be known to have HCV in their systems.  Maybe it enters through sexual, or salivary contact, and then migrates to other tissues, but the virus is always held in-check, at a very low level by the immune system.  In these cases, there would never be a typical blood/liver infection (or nothing detectable anyway).  These people might sometimes exhibit symptoms of chronic illness, or CFS type syndromes, but would not demonstrate obvious liver problems, or blood markers.  The next step in the theory goes:  If some of these 'occult' virus infected people become problem drinkers, abusing alcohol regularly and in large quantities, could they possibly 'activate' the blood/liver infection, thus overcoming the 'in-check' immune system control of the virus???

This scenario would provide an answer to the many cases of HCV that seem to have no 'risk factor' in their etiology, other than the person being a heavy drinker, or having had a severe alcoholic period of life.  I have read about numbers of people who are considered 'alcoholic' drinkers, who end up being diagnosed with HCV.  Could there be a 'latent' form of the virus out there, which only activates under very special circumstances.  One doctor that I met with said that the majority of his HCV infected patients had none of the typical risk factors (IDU, Transfusion, tattoos, cocaine use, needle stick, etc), and that those patients claimed to have no idea when or how they got the virus.  

Anyway, this is very much my own theory, and it is a fuzzy, uncertain theory at best, but I see signs in recent research that there may be some logic behind this proposition.

There are many unexplained autoimmune-related diseases cropping up in recent years, including CFS, Fibromyalgia, Dry eye, severe allergy/asthma, etc.  Could some of this be caused by occult virus, being held in-check by a constantly over-working immune system response (hence, generic autoimmune manifestations)???

These kinds of studies, more than ever, indicate to me that we need newer, and more comprehensive drugs, and real cures, in future decades.  I think we will discover much more discomforting information over the next five years.  For now, we must be happy just to squelch the active blood/liver infection.  That is a huge step forward.  There are many more smaller steps to go, I fear.

Regards,
DoubleDose

[TnHepGuy_]

<u>jmjm530</u> - Thanks for the offer, but I have no way to host them myself. I did do a google, though, and found the papers you refer to on PubMed:

<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14738562&dopt=Abstract">Evidence that plasma concentration rather than dose per kilogram body weight predicts ribavirin-induced anaemia</a>

<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12451285&dopt=Abstract">Dosage of ribavirin in patients with hepatitis C should be based on renal function: a population pharmacokinetic analysis</a>


<u>chriskid</u> - beyond a study center, you're going to be very hard pressed to find any place that would do plasma level testing.


<u>DoubleDose</u> - Yeah, I'm not finding much comfort in any of the studies related to occult. Given the ambiguous findings between studies, I wonder how much is attributable to testing methodologies and testing sensitivites? Speaking of which, I wonder what the current maximun lower limit detection level is when testing for negative strand RNA? Is it possible that with more refinement, more sensitivity, increased amplification techniques, and greater accuracy there will eventually be a higher percentage finding of occult within post-SVR's and spontaneous?

The <a href="http://precis.preciscentral.com/Files/Source/116/AbstractPDF/65594.pdf">Gallegos</a> paper posits a theory of 'balance' between immune response and occult in their conclusion (<i>"It is possible that viral persistence ... may also provide a low level of antigen exposure to keep immune status that would prevent reactivation phenomenon</i>"). If true, anything that upsets the apple cart (i.e. - compromised immune system, etc) could have the potential to cause an 'explosion'. Also, you would think that they could test their theory by looking for the low level antigen response in occult carriers.


TnHepGuy

[DoubleDose]

I agree with your comments. I wonder why more doctors and researchers are not more attuned to these issues, open minded about the implications, and even curious as to how many people are affected, whether in the known HCV infected community, SVR's, spontaneously cleared, or even in the general population.  My speculation is that in the future, we will be finding large numbers of people with this 'low-level' cellular immunity, or controlled cellular infection, who are not typical HCV+ infected persons.  In other words, I truly believe there is an occult version of the virus, outside the bloodstream, that may be more generally out there in the population, within a variety of organs or tissues.  I would think particularly salivary and sexual tissue infections, with very low level antibody activity or cellular immunity.  How about the potential for CNS or gastric infection?  Maybe the virus does not 'explode' in these tissues, as it does in blood and liver infection, OR, maybe it just gets 'attacked' in tissues by the immune system, if it is not initially received directly into the bloodstream...thus initiating a different form of the virus, much like what they are now finding in SVR's, etc.  

Not too far-fetched at this point I believe.

A few years ago, even challenging the 'eradication/cure' nomenclature for SVR's would get you laughed out of any doctor's office.  Now it seems, they are doing an about-face, and sliding into disdained terminology like...remission, de-activation, maintaining undetected viral status, etc.  

I do not think they have clearly explored the limits of this virus, to any great extent yet.  Unfortunately.

Let's hope for some good news.  I am sure ready for something to squelch some of my biggest concerns.  

DD

[couldn't think of a nickname]

I never did mention it before, so you didn't miss it, but here's how it went down:
First, I took liquid herbal extracts of astragalus, milk thistle, hepacure, and I forget what the other was called, but it was a body detoxifier. My enzymes before were about 100 for ALT, and 50 for AST, and this was in 2003. The year before, my numbers were pretty close to normal, as they had been before that. My viral load was about 3 mil. I think. I felt terrible the first 3 days, as I had a healing crisis of sorts. Then, for the next month, I felt better than I had in years. The problem was, my ALT ended up over 200, and my AST over 100, and my vl fluctuated from 7 mil. down to below 3mil. again I think.
I stopped, because my bilirubin at one point went from 1.8 (It is thought I have Gilbert's) to 2.8, and I wasn't feeling that good for a few days-might have been gravel, or not.

Then, I consulted with Dr. Zhang, my ALT was around 240, AST about 120, bilirubin about 1.9. I took AI #3, milk thistle, and I forget what else, but it was his second line protocol-it didn't have licorice root. My numbers stayed about the same, except one bilirubin test showed it at .4 (Gall Formula, just remembered), and I don't recall it being that low before. That ended up back where it started, as I was a non-responder. There are many there who say they have been helped tremendously by his herbs-in numbers, and how they feel. Unfortunately, I was not one of them. His herbs do not cure, although there might be one or 2 who went undetectable and remained so. He uses olivessence to reduce VL.

Since neither attempt worked, I am staying away from everything, hoping I can wait to treat. For some reason, my ALT was over 320 in Feb. and my AST was over 170, but my platelets rose to 224k from 200k. It is those my doc watches the most. My enzymes weren't that bad until I tried all of that stuff, I am almost sorry I did.
I have not had any biopsies. My last ultrasound was 5 years ago when I was in for a gall stone problem (needed endoscopy to push it out of the duct it was stuck in) and the ultrasound didn't show any problems. It was that gall stone problem that led to the HCV diagnosis. Because it was stuck in the duct, my bilirubin was 12, so they tested me for A, B, and C. C showed up. The gastro did a complete ultrasound, liver, pancreas, spleen, and there didn't seem to be any issues then. I had ultrasounds every few years prior to that too, because of the gall stones. I had several, but I think they had passed except for that one, which was too big. They were hemalytic stones created by the blood transfusions I received.
I am geno 1b, got it in 1984.
I should add, I just got finished a massage, and we think it is the apple cider vinegar, but again, she went deep, but no pain. In fact, there is a small bruise on my neck, but felt very little when she worked on it. My muscles are still tight, and give me problems, but maybe not as bad as before. We think it is the ACV, and that is the only thing I am taking, and I plan on continuing it.

[jmjm530]

I probably should have specified that that the *full-text* articles are not available on the web unless you subscribe/pay but thanks for looking up the abstracts.

For anyone very interested in the whole riba issue -- and especially for anyone making a tx decision based on these readings --  I highly recommend reading the full-text articles, starting ith the one that caused all the stir 9-months back "High-dose Ribavirn in Combination With standard Dose PegInterferon For Treatment  of Patients with Chronic Hepatitis C."  You can pay for them online, pay less (or free) at a medical library, or contact the researchers direct who often will accomodate.

As some may remember, I was very gung-ho high-dose riba (HDR) when I started treatment.

In fact, the  Lindhal and Company study cited above became public about day three of my treatment. It so captured my imagination that by day 7 I had switched doctors and convinced my new hepatologist to put me on 2000 mg/day of riba in addition to the double-doses of Pegasys.

Further, at one point I considered traveling to Sweeden either for a consult and to take advantange of the special High-Performance Liquid Chromatography (HPLC) blood test that was then not readily available in this country. Without HPLC, any venture into HDR is somewhat flying in the dark as serum riba levels would then have to be estimated by an admitedly (by Lindahal) shaky formula based on renal function, and also upon the severity of anemia. This is not only less accurate judge of serum riba levels, but more dangerous as any mis-judgment could mean transfusion, temporary termination, or worse.

I may post more on my experience later, but for now I'll just say that while HDR didn't turn out to be the right approach for me, I think it still has limited but important merit in certain very hard to treat patient populations who are willing to risk the additional sides of the riba because of advanced liver disease.

While the original study group was quite small (10 patients) those results, combined with other data regarding riba, suggest a window of SVR opportunity. Anecdotally, I've heard of slow responders well into treatment (post week 20) going non-detect shortly after swithing to HDR. I have not heard SVR data back on this group.

That said, I see very little further research into HDR for a several reasons. Primarily because most researchers -- at least the ones I've read and talked to in this country -- are trying to move away from riba not toward it. This is understandable to anyone on tx as riba is one nasty drug :) And then, at least in this country, there are the resources being tied up in all the exciting next-generation drug trials like the protease inhibitors. This is where many see the action and therefore the effort.

On one hand, I think the lack of riba research in this country had done many of us a disservice as I believe many SVR's could have been saved. On the other, my own personal showed how potentially dangerous this approach can be unless under very proper and controlled conditions. And lately, as I head toward the finish line in my own tx, I'm starting to get more and more concerned about the effects of long-term anemia caused by treatment. Most of us are anemic on treatment, whether we take Procrit or not. On HDR, everyone was anemic on tx and more so. In fact two out of the ten subjects required two transfusions each -- but they did SVR. :)

-- Jim

[couldn't think of a nickname]

Funny, I listened to Shiffman this morning on the call, (thank you keep), and he struck me as someone stuck in the current. I agree that docs seem to want to move away from riba, many of you in here that have treated have had an impact on me, and helped me formulate opinions about it. He stated that anemia is only a problem in about 20%, but I have serious doubts about that number. He said this in response to a question about Viramidine. He didn't think it would gain widespread usage because riba has a generic, ins. cos. wouldn't want to pay, and efficacy was similar. He also didn't think docs would prescribe it over riba. When asked if the insurance issues were taken away if he would script it, he said yes. He left out a major point. As I gather from many in here, if you take riba, you will likely need Procrit, Neupogen, etc. So, instead of avoiding the anemia all together, and paying for one Rx, you dose riba and pay for 2 or more. And as a doc, I would want to spare MY patients anemia. He also thinks interferon will always be part of the treatment (maybe, maybe not, too early to tell, but a case can be made against that) but it sounded like he thought riba would always be needed too. I was surprised to hear that.
He was highly critical (not skeptical) of NM283. Yes, it is not the most potent, but his level of criticism did surprise me, and maybe a little too much. When asked if docs would script NM 283 with interferon and riba, even though they aren't using riba going forward, he stated that riba prevents relapse, if there is no SVR, there is no relapse. Until today, I always thought riba enhanced interferon.
He is a well-respected expert, but that call left me more puzzled in some ways than before.

[jmjm530]

Combo is still the standard treatment and riba is let's say the better (or worse) half depending on your individual reaction :)

Riba may indeed be around for a while, but what I've been told is that doctors are looking for ways to get away from it. Not just because it makes treatment difficult for the patient, but it makes tx very labor intensive for the treating doctor, with riba-induced anemia and the resulting sides, etc.

So for this reason and other stated, you don't see too many doctors jumping on the HDR bandwagon although as they say, you never know -- especially if some of the newer, sexier drugs fail to pan out in time.

As to the the peg -- alas it seems that will also be around for awhile but the good news is that if drugs like Vertex pan out, hopefully peg exposure will be dramatically less than with conventional tx.

Among other things, I had serious flare-ups of my psoriasis on tx due to the interferon, not the riba, but things didn't really get bad until around week 20. This alone would make me reluctant to re-treat with traditional combo therapy in case of relapse.

However, if presented let's say with peg in combination with a Vertex type drug and let's say only 12 weeks of treatment -- that would be another story.

Regarding Viramidine, the last time I spoke to my doc about it, I also didn't sense any great excitement but that was a while ago.

Until something really breaks through, skepticism in the medical community will be there and justifiably so. Let's hope Vertex or something like Vertex changes all that and very soon.


-- Jim

[jmjm530]

Do you have a link to that Shiffman call ? Thanks.

[GoofyDad]

Yeah - I've seen similar anemia projections - and I'm like holy-****, who are they talking about? I think Jim or someone posted that anemia in males is defined as hgb <13. My lab pegs the low end of the bell curve at 12. Heck, even strator, our construction-working treatment-prince standard-bearer is probably heading into that range as he approaches week 10.

Anecdotally speaking, I find anything under 50% hard to fathom.

[GoofyDad]

I've been reviewing some of our vx-950 discussions from last week and I noted concerns regarding the viral rebounds presented in sub-optimally dosed groups.

I intitially questioned this too, until I read further and figured out that the rebound occurred only in experimental dosing levels that, in practice,  are unlikely to ever see the light of day. Vertex will probably have an interest in the bio-mechanics of any viral rebounds, but can't see it as an issue that would affect forward momrentum with the drug.  

Antibiotics might be a good analog. Let's say researchers discovered that, at half-dose antibiotics, infections tend to rebound - whereas at full dose they continue a decline towards undetectable levels. The obvious reasonable response would be to dose at full-dose levels rather than getting hung-up on why half-dosing didn't work.

It should also be noted that the new vx-950 delivery protocols promise to double trough serum levels in future trials - further discounting the significance of any rebounds experienced at lower dose levels.

[couldn't think of a nickname]

Check under the thread "News on Tarvacin Trials" below. Towards the bottom, keepsmiling posted a phone no. and pass code. It has less than 2 weeks left.

My HGB is usually between 12.5 and 13.7 due to thalassemia minor, and the 13.7 is actually quite good for me. I seriously doubt the 20% number as well. He didn't question anything about SGP at all, and was favorable to Albuferon, but HGSI says very little, so basically, there was no PR to critique.

I wanted him to address this question: If those who go undetectable at 4 weeks on current treatment are now only being treated for 12 and maintaining a similar SVR, why would the experimental, much more potent drugs need 24-48 under the same conditions (undetectable in 4 weeks or less)? He only slightly hedged on a shorter treatment duration.
The analysts in that call, if they are worth a dime, should have asked, and no one did.

Just my opinion here, but Albuferon looks to be much better than current interferon, but because of the clinical trial timeline, it will take a while before approved. The prolonged timeline is keeping this from those who need it longer than it should. If this were classified as an orphan drug (which it can't by definition), it would be out much faster. An orphan drug for those unfamiliar, is a drug used to treat a very small patient population with an unmet need.

[jmjm530]

I guess it depends what criteria Shiffman uses when he says "problem". I doubt my tx doc considers anemia a "problem" with my tx -- but I've been anemic for most of tx and to me it certainly is a problem.

[couldn't think of a nickname]

That is true goofy, there was no rebound in the TID dose group, which is what was seen in some in vitro trials they publicized 2 years ago. I'll bet there were docs that scoffed at that notion then, too, just like shortened treatment time is being scoffed at by some now.
Shiffman did say that he thought resistance was not going to be an issue and was overdone, especially considering the usage of interferon.

On one of the threads below I posted the PR on VRTX stating that an arm of an in vitro trial showed eradication in 13 days with no rebound, and a 4 log drop in 9 days. It is my opinion that that was used to drive the human trials, and the question was which dose would reproduce what was seen in vitro. That looks to be 750mg 3x daily.

There are reservations about a 3x daily dosing (also raised by Shiffman, but I have seen this elsewhere too), but it is more of a problem the longer treatment is. And, as Shiffman noted, that might be overdone (as far as being slightly off dose time) since interferon would be used also, unlike HIV.

There are so many questions that need to be answered, and I think 2006 should answer some of them.

VRTX has always said that the key to beating resistance was to drive down the virus very quickly. Virus can't mutate if it can't replicate.

[couldn't think of a nickname]

Good point jim, and sometimes I think if it is affecting someone else, it isn't a problem. Ask the patients, they will tell you, like everyone in here has. That's why I would rather hear experiences from those who have been through it than anecdotally.

[jmjm530]

Maybe you've already posted on this but could you please go over your experience with Zang including when you started, what you took, the condition of your liver, enzymes , before and after, etc and any biopsies before and after. Thanks.

[couldn't think of a nickname]

I think Shiffman said as much on the variants also.

I will say this: If I had to take 950 3x per day for a cure, then so be it. I have taken Dr. Zhang's herbs before 3x per day, I took liquid herbal extracts 2x per day (neither worked for me), and I took vitamins 2x per day (made me feel worse). On Zhang's protocol, I was taking 18 capsules per day. If I did it before on a slight chance, I would certainly do it again for a much better chance. It would be great if treatment were 1 month, because I wouldn't want to take ANYTHING longer than I have to, and I am not crazy about injecting myself. For a shorter duration, my doc would probably do it.

Also, those variants were affected by 950. The food issue (enhanced blood levels) might be interesting. I am anxious to see the data from this current 1b trial with those in the monotherapy arm to see if there is any improvement on the 50% undetectable stat. I think that data will be out either in January or February of next year, so it isn't that far off.

Here is pure speculation: In the call, it seems that interferon added about a 1 log drop to both NM 283 and SCH 5(whatever). If it adds 1 log to 950's data, that would be unbelievable.

Remember, in of of SGP's combo arms, 4 of 10 (I think) went undetectable, and no one did in the mono arm. That drug is less potent, but that was still revealing, and I think, good data for SGP. I am sure that exceeded their expectations, but since they don't say anything, I won't put words in their mouths.

[beamishboy]

wow!!-yu guys bowl me over w facts,opinions,citations,studys&.Experience-thank you ..aftr postn yestrday i v foolishly took an xtra cap of riba;it was awful&i had to work at a BINGO fundraiser for my daughter's swimclub..but i really enjoyed the people&distraction(1st bingo-i was virgin)...i am also a total neophyte @ tx  who will not take tx mattrs into hand again..this stuff scares me,as well it shud aftr readin of yr xperiences..i'm havin real trouble w/ the 'occult' aftr svr...the notion of widespread low level residue vl ;the alcohol/binge trigger makes me nervous..i have always had a goodtime when i did up the town....no more....i will dscuss uppin my dose w doc but i am not quite so eagere anymore...thanks to everyone i learn alot at this site..you are an amazing buncha people..the only good thing about hep c

[couldn't think of a nickname]

Good luck on treatment. I hope someday the occult issue is addressed (I guess it needs to be agreed upon first). Maybe someday there will be something that can be done for that as well.

You can be sure that if a new study comes out, you'll see it here. I think they get sent to TnHepGuy first LOL!

Thanks for all the research and links Tn.

[GoofyDad]

Listening to the VRTX call I get the impression that mutation/variants are limited to an identifiable set of variants. It's not like you introduce a PI and suddenly resistant variants heretofor unknown begin massive replication. In fact, I believe they chracterized it as more of shifting in the distribution of the pre-existing variant population the patient was already hoosting. I could be wrong there, and it seems to contradict their position on the need to drive the virus down fast.

On the 3x dosing - with food - I have mixed feelings. On one side, yeah from a patient's perspective that would be hard to adhere to. On the other side I say, so what? Suck it up. ****, if that's what it takes to beat this thing and you can't do it - well.....well... I dunno what.....

[jmjm530]

Thanks for sharing your story. BTW did you see Zhang in person or just consult via the net?

I also had a bad reaction to some Chinese herbs of unknown name and origin about three years ago with my ALT, AST and GGT shooting through the roof. At the time I was going to start treatment but based on my now high enzymes, my hepatologist advised me to wait until they normalized. The food news was they came back down to pre-herbal levels in about 11 months, as my hepatologist predicted.

That said, Zhang seem to enjoy a good reputation from what I hear although have no personal experience. I did ask my doc about him once and the response was he has nothing against any of Zhang's herbs, his only problem is that it may cause some people to delay conventional treatment too long. He indicated that he has seen some of Zhang's ex-patients in the transplant center. This doesn't mean that Zhang's formulation doesn't work, just that it doesn't work with everyone.

I relucant to offer my opinion on your treatment -- not really :) -- anyway, I'm curious why as a 1b you haven't biopsied since you're obviously in watch and wait mode -- or, more specifically, watch and wait for Vertex mode. :)

Some of your pre-tx indicators such as high platelets do sound favorable in terms of lower liver damage, but still, you are male, you are a 1b.

If it were me, I'd biopsy. If I was very much against biopsy, then I'd trot to Boston or Miami and have a Fibroscan. Last choice would be a Fibrosure test. But I'd do something more to help the "watch" part of "watch and wait."

All the best, and once again I'd like to thank you for your participation here and all the valuable info you bring to us.

-- Jim

[couldn't think of a nickname]

Dr. Zhang does have a good rep. as far as I know, and my PCP has seen everything before I've taken it. I did not see Dr. Zhang in person, but had a few consults, and filled out his pre-treatment form. He diagnosed me with cryoglobulinemia, but when I asked my doc, he said he had just tested me for it, and I didn't have it. I don't remember when I stopped taking them, but when my enzymes were their highest, I had probably been off of them for less than a year.

I haven't biopsied because I think my PCP is not a big fan of them, unless necessary. He looks at platelets first and foremost, and also the ALT/AST ratio. He also palpates the area to check it as well. It has only been a couple of years that my enzymes have been high. I know that is not a good indicator, but my ultrasounds had been good. Biopsies can have risks, and may not be totally accurate either. My PCP has talked with researchers and with Dr. Schiff, and I think his thinking has probably been influenced by the experts he has talked to. He seems quite knowledgable in this area, especially for a PCP, and he even treats it in his office. Some of the tougher ones, he refers to other experts. He has told me about research studies on UV light, etc., so he is definitely not your average PCP. He told me about 3 years ago that protease inhibitors were going to be the treatment of the future, based on HIV work.

Also, I think that I am one who needs to avoid current treatment as much as possible. I think I have risk factors that can cause me problems, such as thalassemia, and maybe an over active autoimmune system as I have always had allergies, and now some asthma, etc.
When I had my gall stone issue addressed, the gastro did want a biopsy, and he was referred to me by my PCP.

I should also add that even as a 1b male, my age of infection was 16, which from what I have read, is not as bad as getting it much later in life-stronger immune system, etc.

I am curious......why did your hepatologist say your enzymes should drop in 11 months (or so)? I am hoping that will happen with me after I remain off of everything for a while. I also had to stop the vitamins I was taking in spring. Believe it or not, I felt worse on them, and felt better when I stopped. I started getting anxiety/panic attacks, my muslces hurt more, I felt weaker, I ate less, I was more depressed, I lost some weight. Since then, (knock on wood for all of these) the anxiety attacks have stopped, my muscles have improved (ACV I think deserves credit), don't feel as weak, the weight is back on, not as depressed. The vitamins did NOT have iron, but I have read that vitamin C can cause iron to bind in the liver if the dose is too high. I don't know if that happened, but all I know is there was a difference.

Oh, I also have Dr. Zhang's book too. He never has claimed to cure it. His only goal is to help keep the liver healthy. Seems like everyone else peddles their herbs as a cure. I am in contact with someone who recently saw him in person, and he was very hopeful about 950 and is well aware of it also. I believe his desire to help is sincere. I was just a non-responder.

[jmjm530]

My hepatologist at the time said the enzymes should eventually come back to baseline but not to treat while they were so elevated. He didn't predict "11 months" but that's what it turned out to be.

-- Jim

[couldn't think of a nickname]

Oh, I see, thanks for the clarification. My PCP told me that, too, but it hasn't happened yet. Of course, my last test was in Feb, and it was likely too soon.
How high did your numbers get, and how much did they go up, if you don't mind me asking?

[jmjm530]

See thread above "Is shorter treatment possible for geno 1's" for more details on what happened with my numbers. In the course of the discussion, I referenced your story in this thread. I hope that is OK.

-- Jim

[couldn't think of a nickname]

no problem, I will look. Sometimes I don't read everything (and I miss older threads).

[jmjm530]

Oh, and the "86" was an AST value, not an ALT value, as stated.