riba concentration instead of dosis

http://tinyurl.com/6759rg

The ribavirin bioavailability of ribavirin can differ between two persons, even if they have the same height and bodyweight. Hence it just seems to be consequent to individualise the therapy more and more and to adapt the ribavirin DOSIS dependent on the individual CONCENTRATION.
I predict a routine testing of riba-concentrations and individualised variation of dosis in a few years.

Regards, drofi


Prediction of sustained virological response by ribavirin plasma concentration at week 4 of therapy in hepatitis C virus genotype 1 patients. Maynard M et al., 2008.

BACKGROUND: Pegylated interferon/ribavirin combination is currently the standard treatment for chronic hepatitis C virus (HCV) infection. Body weight adjustment of ribavirin is crucial for response. However, previous studies found no relation between ingested dose and plasma concentration. The aim of this study was to define the ribavirin trough plasma concentration at week 4 (W4) associated with sustained virological response (SVR). METHODS: Thirty-one HCV genotype 1 patients (8 naive and 23 non-responders to a previous pegylated interferon/ribavirin therapy) were treated with pegylated interferon/ribavirin and assessed by HPLC for ribavirin plasma concentration at W4. RESULTS: Eleven patients (35%) achieved SVR, whereas 20 (65%) were non-responders. The median ribavirin plasma concentration at W4 (1.90 mg/l) varied from 1.62 mg/l in patients with subsequent non-response to 2.28 mg/l in sustained responders (P=0.007). Receiver operating characteristic curve analysis indicated that the 2.01 mg/l threshold gave the best sensitivity and specificity (73% and 80%, respectively, area under the curve =0.80; P=0.007). Sixty-seven percent of patients with median ribavirin plasma concentration >2 mg/l achieved SVR versus only 16% below this level (P=0.007). Multivariate regression analysis indicated that a ribavirin plasma concentration >2 mg/l at W4 was associated with SVR independent of gender, age, weight, baseline viral load and response to previous therapy. CONCLUSION: These results, which remain to be confirmed in large clinical trials, highlight the potential relevance of ribavirin plasma level monitoring at an early stage of treatment. This monitoring could be of help in guiding antiviral therapy by offering dose adjustment in patients with ribavirin plasma level below the 2 mg/l threshold.

[Marcia2202]

So the question would be. How does one ensure to keep a high concentration? Is it through adequate intake of fat with the riba, so the body absorbs it better and it stays there? Rather then upping the dose and risking anemia???

Just a thought...

Marcia

[Marcia2202]

btw.... very interesting!!!

[Proactive]

Thanks for the post drofi, as you probably know, I'm a firm believer in the highest dose of riba one can toterate..This just furthers my opinion, as did  Scherings recent data regarding the low dose riba arm, and vertex's early trials with varying riba arms..
Unfortuantely ribavirin plasma level testing is not common, and probably would not be considered not cost effective for soc treatment..Not to mention, the logistics of finding somewhere to have it done!!!
I was hoping comeagain would posts his actual serum levels, I believe they have been tested in the trial he's involved with..
pro

[Marcia2202]

I so agree with you. Even if they have the equipment at the hospital (I'm in DK) one doesn't know if they would be willing to test the serum level.

So what could one do in this situation to ensure a high serum concentration, not being able to measure it????

Marcia

[Proactive]

As for myself, I was on 1600 mg/day...20 mg/day/kg from week 12 to wk 72 (hovered around 77-78kg during treatment)..hgb held around 11 last 6 months of tx..but at the beginning, I held strong at 14 hgb on 1200mg/day, 12-13 hgb at 1400mg/day (increased at wk 8) and 11-12's hgb at 1600mg/day (increased at wk 12)....I was a slow responder, (cleared at wk 18)...so would I have cleared earlier on a higher 4 week dose of riba? imo, yes...

[Proactive]

There in lies the problem! (vbg),,
I probably should add, so as not to confuse neg virus level with end game svr...still waitng on the 6 month post mark....
Hi ho,hi ho, off to work I go...............;^) pro

[comeagain]

Yesterday i added in my profile that although 9kg lighter and 400mg more riba aday my hgb is pretty much the same as first tx around 125.

I´m in a danish study right now for relapsers geno 2 and 3 ( I`m a g3 ) they are checking the riba concentration in the blood in this study but the result will not be reveled until the study is finished about year from when I have stopped at december 10 .

I´ve already started to worry if I´m gonna make it this time, and this report provided by drofi didn´t make the worry less let me tell you.

But I was <15 iuml at week 4 and I´m doing 48w instead od 24 hope that will do the trick,
It seems like there always a catch by participaiting in a studie the catch here is that I cant change my doses .

ca

[comeagain]

I have added fat when taking the riba this time which I didn´t first time, maybee not enough though i take it with 20cl yuoghurt 3% fat  at firs i took peanut butter  but stopped that after a couple of weeks.

[jmjm530]

Marcia: How does one ensure to keep a high riba concentration?
============
For a number of years, the Sweeds (Linahl and Company) have been advocating riba dosing by pharmokentic formulas both based on renal function and more accurately by HPLC (high performance liquid chromotography) serum testing. Their work culmunated in the famous High Dose Riba pilot study three years ago where they achieved close to 90 per cent SVR in ten subjects in 48 weeks using conventional Peg doses.

When I treated three years ago, there was no HPLC testing available in this country and my plan was to have it done in Sweden, but significant anemia made it a moot point.

As to the future, based on conversations with a few liver specialists, I don't see HPLC testing (or HDR) as a priority since efforts and funds are elsewhere such as with the exciting PI's. I see this as both good and bad. Good because HDR does not come without its costs in terms of sfx. And bad, because proper riba dosing could make a big difference for many on SOC who need it. I've felt for years -- and Lindahl stated in kinder words --  that dosing riba by weight alone is pretty crude. And while riba dosing has been getting more attention and importance over the years, one wonders why at least *someone* isn't doing HPLC serum testing here on a clinical level. Or maybe they are since I last looked into it.

-- Jim

[jmjm530]

Forgot to add that one available method of determing riba concentrations is by carefully plotting hemoglobin response, as some suggest a relatioship between anemia and riba concentrations. While available, it's still somewhat crude and potentially dangerous since there's 2-4 week lag in dose changes and hgb response. One can -- and I did -- therefore get into trouble using this approach by titering up the riba too fast. Still, if one notices almost very little  hgb response at let's say week 4 -- and if viral load is still not UND -- upping the riba would be something I'd personally discuss with my doc.

[drofi]

Hi,

determination of ribavirin concentration in serum is available as a daily service with next day results from several labs in Germany, eg http://tinyurl.com/6auaex
The costs are low, 53 Euro / determination.
Although the USA are a less developed country :-) , measuring ribavirin should be possible and available there too.

drofi

[mremeet]

"So what could one do in this situation to ensure a high serum concentration, not being able to measure it????"

Personally I would (1) take the riba with plenty of fat every time, (2) if my HGB stays above ~10.5, I'd increase the standard dose (within reason) until I was hovering around 10 (as long as I could tolerate the sx). And (3) if my HGB was below 10, I'd get on Procrit in order to prevent a dose reduction.

I think this is about the best you can do in practical terms. Because if you were doing everything spelled out above, even if you did have blood serum data that showed you to be below the optimum concentration, there isn't a whole lot you could do about it anyway (beyond what is spelled out above).

[jmjm530]

As stated, its not  the last time I checked which was about a year ago.

BTW neither of the two "tiny" links you posted work. And I thought everything was supposed to work in Germany? Oh, maybe that's in Switzerland :)

[jmjm530]

I'd modfity Mre's good suggestions a little and base the "target" hgb level on a pre-determined drop (say 2-3 points) and symptons (how you feel) as opposed to a set number such as 10.5.  In my case, I never would have been able to function at 10.5 and ended up in the ER at hgb 11.8 early in tx. Still it was close to a 3 point drop from pre-tx baseline in only a few weeks. A more agressive strategy would be to take Procrit (epo) prophalactively and still try and get down to that target hgb level. As stated, the titering up part is a bit tricky because of the delay between increasing riba dose and hgb response.

Here's how not to do it: I started at riba 1200 and decided to titer up to 2000/day based on another strategy which was trying to emulate/catch up with  the Swedish HDR study which got full copy of (including dosing charts) one week after I started tx.
So, day one I took 1400 riba and felt pretty good. Day three I upped it to 1600 and felt no different. So on day four I made it 1800. Then day five 2000/day. A nice gradual titer I thought. LOL. Well I think it was day seven of my plan I ended up in the ER ;)
What I probably should have done was to wait at least a week (possibly two) before increasing the dose.

Just want to add that I'm not advocating anyone go on a HDR strategy or any sort and I think my personal example is one reason how you can easily get yourself into trouble. Nor, is it probably necessary for many, esp geno 2's and 3's. But if you do, just make sure you get your doc on board because you will need frequent monitoring. My doc knew what I was doing, went along, but probably should have given me sterner warnings not that I would have listened at that point :)

[nygirl7]

I took Jim's advice when I joinned the forum because I was nutso that I was a geno1a and geno1b and it was going to be harder to achieve SVR (even though the doctors said it would be just the same I didn't believe them).  My weight based would have been 800 however I started off with permission to take 1000 a day and started instead on 1400 and worked up from there to between 1600 (double riba).

At week 2/3 I had a SIX POINT drop in my hemoglobin in just over a week.  It was devastating. However I did not dose reduce and instead added procrit (which had a heck of a time keeping my hemo up because I was on SO much riba). I am that adament and believe that a dose reduction can easily lead to breakthrough.

I only say this because since I hit it so hard and so furiously - it appears to ME that the serum level reaches it's max point somehwere (at least for me) around the week 2/3 mark. At that point I almost hit UND at week 4 and  had over a 3 log drop. I wish there was a study that would show when it reaches it's height!

So testing on myself I'd say going by the riba serum level = hemo drop theory...that it is absolutely correct.

Would I advise anybody else to do it?  No not quite so hard - I'm bullheaded and with the help of people in here didn't quit treatment but it was close. The six point drop in just over a one week period was too physically difficult for anyones body to handle.

I definitely and totally advise taking the top level of riba that you can though.

Just my humble observations.

[Marcia2202]

Thank you, very interesting...

Of course one would want to have the doc on board with either upping the dose when the serum levels drop etc...

Plotting hemo response sounds quite complicated to me and I don't think I would attempt doing this, having read what one has to take in consideration and that it seems to be quite inaccurate.

Marcia

[Marcia2202]

That's exactly what I was looking for... a practical solution to this problem...

I was suspecting the high fat. Wouldn't one have to maintain a certain amount of fat all throughout the day then, to keep the absorption level at a certain degree???

It makes me think of the theory you posted on the other thread... stuffing oneself with fat all day... maybe you have a big point there. Maybe it's not only the high cholesterol, but maintaining a high level of fat throughout the day.

Those riba pills, don't they have a quite thick coating around them and thus stay in the intestines for a looong time. Are they time release??? Just wondering about the long half life of the riba. The stuff in them is definitely lethal. One is in no way allowed to break them in half or take them if they are damaged. On the Danish insert it even says that if your skin comes in contact with a damaged pill, you should wash the area thoroughly with soap and water.

So back to the practical.... If your hemo levels don't go down like crazy, is that always a sign the riba isn't doing it's job? Aren't there some ppl who's hemo just kind of stays in normal range, not needing procrit and tx is working for them anyway?
There must be ppl who SVR without ever having had to take procrit.

And what if your doc doesn't agree to upping the riba?

Marcia

[mremeet]

I wouldn't overanalyze the situation. You are geno 3, you're thin and in great shape with probably minimal liver damage. So you have a much larger margin of likely tx success than us downtrodden geno 1's. And you have that high margin of likely success by simply playing by the numbers. But the fact remains that about 1 in 5 fail treatment for geno 3 (playing by the numbers) so I would take some basic steps to enhance odds, perhaps including adding a little more riba into the mix (as described above). But if I were you, being geno 3 I'd take a look at what gauf is doing (also geno 3). You do know about alinia right? And you do know of the amazing test results from an alinia trial (for geno 4) in Egypt? (with additional supporting evidence from other sources suggesting it's also effective on all genotypes) And you do know that alinia essentially has no side effects and is already available off the shelf? Also take a look at PPC that HR has discussed here (also in gauf's regimen). PPC has been shown in a reputable german study to enhance SVR rates when dosed in combination with SOC. And again, no side effects and very safe profile.

But yeah, if I were you I'd get on the saturated fat and attempt to elevate LDL cholesterol to higher levels prior to tx, especially if you have very low cholesterol (which you may have considering your uber-healthy diet). The data for high pre-tx LDL levels and SVR rates is pretty overwhelming, and there is a reasonable rationale explaining why that may be. Also it does tie into taking the riba with plenty of fat, so the two strategies sort of work together.

You ask about how quickly the riba is absorbed into the body. Speaking for myself, I could feel the effects of the riba within an hour or two after taking it. Like clockwork, my scalp would tingle and I would feel a little more edgy shortly after taking it. So although it does have a long halflife, I do believe that a short term run-up in serum concentration still occurs after taking the pills on each dose. The danish insert sounds a bit "legalestic", if it were that dangerous and toxic I'd be dead right now. I was swimming in it for almost a year and I'm still here. Not to suggest you shouldn't take it as directed, but the warning sounds a little over the top considering you orally ingest it 2 or 3 times a day for months and months and months while taking it with fat to improve its absorption.

You ask "If your hemo levels don't go down like crazy, is that always a sign the riba isn't doing it's job?" I really don't know in every single case, but generally my gut sense is that generally this is true. Ribavirin has a direct effect on HGB levels. If I were in tx again and my HGB was like 12 or something, I'd seriously look into taking more ribavirin. My personal anemia tolerance threshold was right around 10. Some people can handle more or less than this. I would adjust riba to sustain a HGB of around 10 as long as I could tolerate the worst of the side effects (which for me was rash). For me the rash kept my dosage at a level that equated to an HGB in the high 10's, low 11's.

And if your doc doesn't agree to upping the riba, then that's something you'll have to figure out for yourself. There is sport in this game, and quite a bit of it at that. ;-)

[drofi]

Hi Jim,

sorry for the wrong links. Btw, tinyurl is from Gilby, a guy from Minnesota.
http://www.gilby.com/whois.html

I knew it could NOT be from Germany or Switzerland :-)

Best, drofi

[Trinity4]

Reading your posts now with such a conservative approach, it's hard to imagine you taking such risks.  Given the fact you seem to have been much more effected by the sx than most, I would have thought risk taking wasn't a part of you MO.  But I guess we learn by our mistakes.  Personally, I don't want to juggle the riba around.  Numbers are holding steady on the low side and want to keep it there  -  I just think it's too dangerous to over medicate. Presdosed Riba for a week prior to tx - wasn't UND at 12 wks so who knows.
Trin

[jmjm530]

Drofi,

Yeah, but isn't Minnesotta well represented with German immingrants :)

---------

We've had this discussion before re raising LDL and my thoughts are that it's probably an association between high LDL and SVR and not a cause and effect. In other words, given an average base diet, those with higher LDLs may have more liver damage and/or other receptor issues which may affect treatment. For that reason, I don't advise pigging out prior to treating, although in your case -- given that you're thin -- probably won't matter as long as you don't increase your BMI. No studies I know of to support the LDL thing conclusively so not saying I'm right and anyone is wrong here,  but there studies are clear that lower BMI is associated with SVR. So, eat all the ice cream you want, just stay thin (and female) two things in your favor not to mention your genotype! Also, as Mre says, don't go too crazy with the riba given your genotype, etc, as you can't SVR unless you stay with the program (don't drop out with sides) or are very lucky.

[jmjm530]

Trinity: Reading your posts now with such a conservative approach, it's hard to imagine you taking such risks.  
---------------
Your're probably talking about my bent to a "watch and wait" approach for those without significant liver damage.

This is a *pre-treatment* stance, not a treatment stance, and is consistent with how I made my decision to treat. I "watched and waited" until I was told I was between stage 3 and stage 4 before I treated. Not suggesting anyone else wait that long, but that's my story.

Treatment is an altogether different story, and I've always advocated an agressive approach in selected populations -- especially genotype 1's with significant liver damage, which was me when I started treating. You're relatively new here but I've been posting about agressive stategies such as double-dosing, extending treatment, and higher doses of riba before any of them became popular and in fact was the first person in the forum to mention pre-dosing riba, as far as I know.

So, yeah, I'm "conservative" in the sense that I feel people should wait if they can. And also somewhat conservative as to how "hard" someone should try during tx if they have little or no liver damage. Or if they're a genotype 2 or 3. But no, I'm b*lls to the w*lls for those with signficant liver damage who really have to get rid of the virus now. That doesn't mean one should be reckless and that's why I tell my ER story because I was a bit reckless with the riba myself.

-- Jim

[mremeet]

The referenced study pretty much covers (and allays) your concerns regarding a possible correlation between advanced fibrosis and a decrease in cholesterol. As I suspect you already know, cholesterol production in the liver is not usually significantly curtailed unless cirrhosis is well advanced (at least from what I've gathered over the years). And as you know SVR rates in regards to fibrosis have fairly recently not been shown to decrease unless you have cirrhosis (as you often point out here on this forum). Less than half of the referenced study participants had F3 or F4 fibrosis. And therefore, to suggest or imply that the data displayed in the study is really just "re-discovering" a correlation between poor SVR rates and cirrhosis is in my view incorrect. Especially when the stunning EVR and SVR rates are revealed for those with high LDL levels. Here's a few excerpts:

"Univariate analysis using age, gender, fibrosis stage, viral load, ethnicity, and steatosis as variables showed only age and genotype to have a significant relationship with treatment outcome. Multivariate exact logistic regression analysis evaluated the effect of pretreatment LDL and cholesterol levels on treatment response after controlling for age and genotype…The statistical significance of differences between responders and nonresponders in LDL and total cholesterol levels remained after controlling for these confounding variables."

and...

"Among the variables considered to affect treatment outcome, including genotype, stage of fibrosis, steatosis, age, gender, and viral load, only genotype and age were associated with SVR."

and...

"The presence of severe fibrosis was shown to be an independent predictor of SVR in IFN-based therapy for patients with chronic hepatitis C.[19] There is a decrease in serum cholesterol and LDL levels as the severity of liver disease increases.[20] Thus, the inability of patients with low LDL levels to achieve SVR could be secondary to advanced liver fibrosis. However, this effect is unlikely to completely explain the observed association because the effect on cholesterol is generally seen only in very advanced disease. Patients with HCV genotype 2 or 3, most of whom achieve SVR and are thus treated empirically, accounted for about half our study population. Thus, unlike patients with genotype 1, liver biopsy is often not performed in patients infected with non-genotype 1 HCV. A chi-square test with available data for stage of fibrosis and SVR, however, did not show any significant correlation. Therefore, fibrosis stage was not included as a covariate in the multivariate analysis. Among those patients with genotype 2, LDL level remained a significant prognostic indicator for SVR."

As to the rest, the evidence in this study very strongly suggests high LDL levels DO increase EVR and SVR rates *substantially*. Here's just a few blurbs:

"LDL and cholesterol levels prior to treatment were found to be higher in patients with positive EVR, ETR, and SVR. This difference remained significant independent of age. Multivariate analysis controlling for genotype and age showed that the higher the cholesterol and LDL levels prior to treatment, the greater the odds of responding to treatment...In conclusion, having higher serum LDL and cholesterol levels before treatment may be significant prognostic indicators for treatment outcome of those with chronic hepatitis C infection, particularly in genotypes 1 and 2."

"When we observed the effect of pretreatment LDL level, controlling for age and genotype, we found the odds of patients in the medium LDL group achieving EVR was 2.43 times that of patients in the low LDL group. Similarly, the odds of patients in the high LDL group achieving EVR was 2.43 times that of the patients in the medium LDL group. Likewise, looking at the effect of pretreatment cholesterol level while controlling for genotype and age showed the odds of patients in the medium cholesterol group achieving EVR was 1.93 times that of patients in the low cholesterol group, and similarly, the odds of patients in the high cholesterol group achieving EVR was 1.93 times greater than patients in the medium cholesterol group."

"...Multivariate analysis of serum LDL level and SVR, after accounting for age and viral genotype, showed patients with higher LDL levels had significantly higher odds of achieving EVR, ETR, and SVR. Similarly, higher pretreatment serum cholesterol level was associated with higher odds of having EVR, ETR, and SVR."


Marcia - They do go on to explain some special situations pertaining to geno 3. But still IMHO it seems advisable to temporarily increase LDL levels prior to and during at least some of your treatment:

"We found a higher prevalence of steatosis in patients with genotype 3 than in patients with genotypes 1 or 2. The sample sizes in this study were too small to analyze the effect of steatosis on treatment outcome in patients with only HCV genotype 3. The mean pretreatment LDL levels for genotypes 1, 2, and 3 were 100.1, 122.7, and 91.1 mg/dL, respectively, and a similar pattern of results was found for total cholesterol level. This is consistent with previous studies that showed a high prevalence of hypobetalipoproteinemia and steatosis in genotype 3-infected patients.[21-23] The rates of SVR in patients with genotypes 1, 2, and 3 were 39%, 85%, and 53%, respectively, in our study. Thus, having higher LDL or cholesterol levels prior to treatment might indicate a good outcome only for patients with genotype 1 or 2, not for patients infected with genotype 3. This could be a result of alteration in beta-lipoprotein metabolism induced by genotype 3a by interfering with the synthesis of cholesterol in hepatocytes.[21] Although the pretreatment LDL and cholesterol levels were low in patients with genotype 3, those who achieved sustained viral response seemed to have comparatively higher LDL and cholesterol levels than those who did not. The same analysis could not be done for EVR and ETR as our data were biased toward responders, and an analysis with a larger cohort of genotype 3 patients would be needed to further evaluate this in future studies."

[mremeet]

Oh yeah, here's a link to the study if anyone wants to read it in its entirety:

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

[jmjm530]

Thanks for the clarification, it's been awhile since I've seen the study. Still not convinced that intentionally raising LDL will be an effective strategy even if the correlation is not with lack of advancing advancing fibrosis as there could be other correlations/factors.  

Still, might be an interesting study and/or a question to pose to Dr. Dieterich (he's handy :) ) or some other researcher. This current article somewhat supports your proposition although they are proposing using a drug to raise LDL.
http://www.aidsmeds.com/articles/hiv_hcv_hepatitis_1667_14560.shtml

Anyway, thinking about it some more, I think your approach quite reasonable pre-treatment as long as LDL could be raised without increasing BMI which I'm sure could be accomplished with a careful diet.

Ironically, some other studies suggest that statins can also positively affect SVR
http://www.hivandhepatitis.com/2007icr/ddw/docs/052507_a.html

so I guess that would put one in a quandry of which route to go!

[Marcia2202]

I'm just posting this again.... I had posted it on my thread, where we were having the same discussion and these were my answers and questions to your post. The first part is regarding fat and coagulation and the second part is the cholesterol bit we are talking about here.


Thanks for posting that again and explaining it to me further.... especially the part with the saturated fat...  (I always kind of get stuck on the word 'aggregation', kind of go blank about the meaning, maybe because it kind of reminds me of aggravation)  :-)
What you posted applies to nonvegetarians...

*Lactovegetarians have altered platelet linoleic and arachidonic acid concentrations in comparison with nonvegetarians.*

Could you please explain how the above sentence  relates to the literature you posted, as that is what I am... a lactovegetarian...So I wonder if we metabolize foods in a different way, or if this can be applied to lactovegetarians.

I'm sorry, if I might seem a bit dense, but I am kind of brain fogged since yesterday again. And I don't seem to be able to make sense of it.

I must say that I am a total fan of Virgin Coconut Oil and ONLY cook with it, but in the last month, I have somehow not used as much of it as I usually do.  Go figure... maybe that is the culprit...

Thank you soooo much for pointing that out to me. I was already planing to have a table spoon of it with my riba twice a day. Maybe I should already start now doing this. It's also great in smoothies.

VCO is a saturated fat, but a 'good' one. It doesn't up your cholesterol, BUT is actually said to lower it. So I don't know how that would fit in the cholesterol theory. My cholesterol level is 4 SI Units, which is the equivalent to 154.44 in the units you use in the US. So it is in the medium range, I believe.

Thanks for the link... very interesting... It looks like it might not really apply to me though, as I am a 3a... I wonder if it has to do with ca 70% of us 3ers having viral steatosis.

*Thus, having higher LDL or cholesterol levels prior to treatment might indicate a good outcome only for patients with genotype 1 or 2, not for patients infected with genotype 3. This could be a result of alteration in beta-lipoprotein metabolism induced by genotype 3a by interfering with the synthesis of cholesterol in hepatocytes.[21] Although the pretreatment LDL and cholesterol levels were low in patients with genotype 3, those who achieved sustained viral response seemed to have comparatively higher LDL and cholesterol levels than those who did not. The same analysis could not be done for EVR and ETR as our data were biased toward responders, and an analysis with a larger cohort of genotype 3 patients would be needed to further evaluate this in future studies.*

But I will up my cheese intake... for eating it with the riba breakfast.

I went out to have a delicious ice cream a few weeks ago and I could only eat about 8 spoons and had to throw it out. But who knows, as many people say that their taste changes on tx, I might become the junk food nut instead of the organic vegetarian health food nut. If I can find organic junk... :-)

I hate ice cream.....

I hope that my post made sense.

Marcia

[Marcia2202]

Thanks... My BMI fluctuates between 21 - 21.5, so putting on a few kilos would probably do no harm. But it would be difficult for me to start pigging out. I am so not used to that and I don't think I would be able to handle pigging out. It makes me feel sick in my stomach for hours and I get cold sweat outbursts, especially with warm milk. Be it in tea or hot choco, etc. I can take all kinds of raw milk cheeses without any problem.

As to upping the riba, my doc is not keen on that at all.. she wants to treat me with 180 peg and 800 riba, which is weight based. (I weigh between 56 -58) I think I would be too chicken to up it myself, without my doc's consent.

That's why am was asking about a natural way to keep the serum levels up there, as there will be no way of monitoring the serum levels.

Marcia

[jmjm530]

The only way I know of to potentially maximize serum riba levels (without an increase in riba dose) is to take it with a very high fat meal which is better defined in one of the package inserts somewhere. You probably also would be wise not to take any fiber supplements -- flax, bran, metamuscil, etc -- withing 2-3 hours of the riba. Same with antacids such as tums, maalox, etc.

[jmjm530]

You mention that your doc won't let you pre-dose the riba, but maybe you can negotiate starting it the morning before, the night before, or at least the morning of your first injection. The latter being standard although some are told to take the first dose that evening. Dr. D. had some favorable comments on pre-dosing in the professional forum. Maybe you can print it out and discuss with your doctor.

[Marcia2202]

Thank you Jim

Already tried to discuss with them... no predosing. I remember Dr. D's comment all too well, as it was my questions he answered regarding the subject.

*We usually use pegasys with weight based ribavirin. I might tend to use more ribabirin on geno 3 since it is slightly more difficult to cure than is geno 2*. ....and......
*There is no data yet on predosing with RBV, but I am getting more convinced of it and would do it myself if I had to start again.*

I will start taking the riba the day I start the injections, meaning that i will either take riba once or twice before my first injection. That depends on what time a day I plan to take my first shot. As I will only get the meds around 11 am, on day 1, I will take my first riba at 12 noon and the second one 8 hours later. I was going to take the shot later that night, 'cause it's our wedding anniversary and I don't want to have the chills while we have dinner.
From next day on I'll take the riba in the morning and afternoon. And I think I will be taking the shots early afternoon in the future.

I don't take any fiber supplements not antacids.... so that is already a good point. I will take the riba with a piece of nice Danish ryebread, the kind which is more fatty with sunflowerseeds and a chunk of good raw milk cheese, a tablespoonful of coconut oil and my krill oil gelules. that should be enough fat, don't you think? or maybe I should start eating butter again, haven't done that in years. I could put some butter on the bread, never thought of that.
(raw milk cheese is generally more fatty, as the fat has not been separated from the milk etc.. during the process of pasteurizing and whatever they do with it.

[merryBe]

Boy, that's busting your chops to get somewhere.

You know when I first read the Lindahl study I was all gun ho to get the led out too...
but it took only 3 days to convince my body otherwise.

I think the operative thing is to remember we all want to keep our kidneys and have enough blood to carry oxygen and fight infections as well.
The increased danger didn't really get relayed as well in the study as it should have,
but 2 in 10 renal failures is a LOT.

All this said, I really think the issue here is that early studies showed better results with quickerlog drops, but earlier studies rarely carried tx out longer than 1 year.
Now that it has become apparent that slower response can achieve the same percentages with longer treatment it seems the only case for Riba overdosing is to save the insurances some money. I think if one can treat without totally deteriorating the system, then the case for both weight based and extended treatment make even more sense, because the idea of doing the least harm should be part of the equation.
mb

[Mr Liver]

I have read a few of the studies regarding the subject of ldl and statins, but nothing recent. I believe a couple of them theorized about the association between lipids,hcv,and statins. In short, and according to what I recall, all cells have receptor sites for lipo-proteins (they carry the lipids). These same docking sites are used by both hcv ( fits just like a glove I'm told ) and statins. When statins occupy these sites neither lipids nor hcv can gain entry. This accounts for lower cholesterol and as some studies have shown anti-viral properties displayed by a statin.  When lipids reside on these receptor sites, hcv cannot gain entry there, and unless a suitable host cell is found soon enough, either natural viral decay or elimination through immune mechanisms is more likely  to occur to the circulating virus. In theory this is what may account for the higher ldl values correlating to svr, as the blocked receptor sites on host cells (predominantly hepatocytes) helps to prevent hcv from docking and gaining entry for the purpose of replicating itself. The correlation between svr and vl at all points (not just pre-tx) is well known. In theory anything which slows the replication rate of the virus has a potential to effect more positive end results from tx. If anyone has a different take based on the studies, please chime in.
ML

[Marcia2202]

Highly interesting!!! Thanks for sharing that!

Marcia

[mremeet]

Yep, although apparently the exact inhibitory mechanism is not known with 100% certainty, the LDL lipids appear to plug up the receptors on the liver cells and block access to the virus. Here's what they say about it in the referenced study:

"The low-density lipoprotein receptor (LDLR) has been proposed as a candidate receptor for the hepatitis C virus (HCV). Competitive inhibition of HCV binding to the LDLR by low-density lipoprotein (LDL) has been shown in vitro. If similar inhibition occurs in vivo, an elevated serum concentration of beta- lipoproteins may reduce the efficiency of infecting hepatocytes with HCV by competitively inhibiting HCV viral receptor binding."

and...

"In recent years many efforts have been made to identify receptors involved in viral entry into host cells. Two molecules are proposed to function as HCV receptors, namely, the low-density lipoprotein receptor (LDLR) and CD81.[3-5] Experiments in vitro showed competitive inhibition of binding between HCV and LDLR by purified LDL.[3] If similar inhibition occurs in vivo, the serum concentration of beta-lipoproteins may influence HCV proliferation because cell infection is required for replication of the virus.[6] Serum HCVAg levels negatively correlated with serum beta-lipoproteins, supporting the concept that LDLR is the HCV receptor and that beta-lipoproteins competitively inhibit infection of hepatocytes with HCV.[6]"

and...

"The potential involvement of the LDL receptor in HCV infection provides a new approach to therapy in the future. Such advances may include the use of LDL receptor-blocking analogues that may slow viral replication and progression of the disease, prevent reinfection of a transplanted liver, or improve the rate of sustained viral response."

As far as statins achieving the same goal, I've often wondered about that (haven't really been keeping up on this stuff since getting my SVR). I don't know how statins work to lower cholesterol (never researched it). I'm not sure if they somehow trigger the liver to lower its own production of cholesterol (as the lipitor tv commercials suggest), or perhaps they bind to the fat lipids and make them too big for the digestive tract to absorb (similar to the ill fated Olestra several years ago - "anal leakage" anyone? ;-). But I didn't know they actually bind to the same receptors on the liver cells as you state in your post. Not sure how that action would lower cholesterol in the blood, but maybe the feedback signal pathway for the liver to produce cholesterol is sensing how many of its receptors are filled with LDL lipids? I suppose another possibility instead of filling the keyhole would be changing the key. If the virus (or fat lipid) is a key that fits into the keyhole, and a bulky covering could be put over it, that might help keep it from fitting into the keyhole, thereby achieving a sort of mirror image of the same effect.

Whatever the mechanisim, something's up with HCV replication, lipids and cholesterol. There's a connection here that can be exploited and manipulated for helping to cure HCV. Some of these statin research papers have been saying that statins can be even more effective than ribavirin as an IFN adjunct. If true, that'd be the first "herbal" substance I've heard of that has a very real potential for helping people become cured. By that I mean I've read some of jim's past posts on statins and how "red yeast rice" apparently has the same active ingredient as lipitor (if memory serves). So maybe someday a treatment with IFN and red yeast rice will cure more people than IFN+ribavirin? That'd be nice. Anyway, I did a quick search and found a few tidbits on statins and HCV:

http://www.hivandhepatitis.com/hep_c/news/2006/071106_a.html

"The authors concluded that statins, especially fluvastatin, "could be potentially useful as new anti-HCV reagents in combination with interferon." In fact, they suggested that fluvastatin plus pegylated interferon is more effective against HCV than pegylated interferon monotherapy or pegylated interferon plus ribavirin.

The reason for the statins' inhibitory effect on HCV is unclear. The statins did not kill the host cells, so the anti-HCV activity was not due to cytotoxicity. The fact that pravastatin did not inhibit HCV replication despite its effect on HMG-CoA reductase suggests that the anti-HCV activity of the other statins is not directly due to inhibition of HMG-CoA reductase.

The researchers suggested that "the statins possess the ability to inhibit the replication of HCV RNA via a specific antiviral mechanism." The statins' anti-HCV activity was reversed by the addition of mevalonate or geranylgeraniol (two compounds that play a role in the HMG-CoA reductase biosynthesis pathway), suggesting that inhibition of these proteins may somehow block HCV replication.

While this research is still in the preclinical stage, it suggests that statins may in the future be used in hepatitis C treatment regimens with interferon, either in addition to or instead of ribavirin and experimental agents - such as protease and polymerase inhibitors - that directly target HCV."

[jmjm530]

Mre: By that I mean I've read some of jim's past posts on statins and how "red yeast rice" apparently has the same active ingredient as lipitor (if memory serves).
-----------------------------------------
Same as Lovastatin (Mevacor®), another statin. As a side note, my cholesterol went down dramatically during treatment, only to return to pre-tx (perhaps even higher) levels after stopping treatment. It's academic for me now, but given this new research, I'd probably go on statins (or Red Rice Yeast) pre treatment for it's potentially anti-HCV effects.

[mremeet]

Maybe going on statins while eating hamburgers every day would be the REAL creme de la creme?? Sounds good to me!

[jmjm530]

That was the dilemma I posed earlier regarding two possible pre-tx strategies --- LDL loading (pigging out) versus statin loading which should result in LDL reduction, (regardless of how many hamburgers one eats) at least that was my experience when I went on a decent dose of Lipitor.

Maybe McDonalds and Pfizer (manufacturer of Lipitor) will run respective trials to find out.