Question about anemia and viral load response

[susan400]

Does how soon you get anemic, have any bearing on your viral load?  My hemoglob., and RBC, had started to get lower, below normal on the lab cutoff and then, w/o my doing anything (i.e. no iron, no Procrit), it came back up on it's own.  Now, mind you, I don't want to particularly be anemic, but I had heard that if you get anemic that you have a better chance at clearing.  Any thoughts on that?  I am a little over 8 wks in.  On 1000mg of Riba a day.

Susan400

[coeric]

Flcyclist also describes going on long bike rides, and he did not experience much hemoglobin drop.  You are an inspiration to the rest of us, and thank you discussing your exercise regime.  
Blessings
Eric

[susan400]

Yes, I do force myself to exercise, usually daily, if not, like 6 days a week.  Right now, it's not to the same degree that I was prior to TX, but I have a treadmill and a stationary bike at home and 2  3-lb hand dumbells.   Usually, I take my book and put it on the book holder on my treadmill and read while I walk on it.  I start off slow and try to very gradually increase it.  If I start to feel to winded, I back it down to a slower pace.  It helps me to keep from being depressed because I don't do Anti-D's and really helps me alot with sleep and muscle/bone pain.  It tires me out alot and I can't do it in the morning because after the morning Riba (6:30 am) I take the 3 pills and 2 hrs later I'm wiped out.  So, I do my exercising in the late afternoon, before my 6:30 pm Riba dose.  I normally wait for the exerising until around 3:30ish.   So, maybe it's why my hemo is higher?  


Susan400

[eureka254]

the above should read:  "not having drastic anemia does NOT preclude good response."

[coeric]

One the Ribavirin concentration study docs in Denver told me that they do not see as much anemia in Denver as is reported in folks living at lower elevations.  I wonder if there is also a relationship with cardiovascular fitness and anemia.  I believe in one of your earlier posts you mentioned engaging in regular exercise. Perhaps regular exercise helps with red blood cell production and you do not experience as much anemia.
Blessings
Eric

[eureka254]

"I'm going to try not to read too much into this."
-------------------
Hard to do for sure, but sometimes it's the best course of action.  Being blinded really leaves you without much wiggle room, and the lack of information about your status doesn't really provide the option for you to make any good conclusions.  

It's so easy to over-think things, but gotta keep positive: not having drastic anemia does no preclude good response... lots of folks get that SVR with no anemia... keep and hold that thought.  

I know you've been one of the toughest warriors fighting against hcv and with all my heart I wish you success in reaching SVR this round... you so very much deserve to win.  Best wishes to getting to and staying undetected forever!! ~eureka

[susan400]

I am in a blinded trial so I have absolutely no idea whether my viral load has gone down or not.  I won't know if I'm allowed to continue or if I've had a good enough response until week 13, based on week 12 labs.  I was just concerned because of the hemoglobin not dropping and worried about the Riba not getting absorbed.  Unfortunately, since I'm in a trial and they count my pills on every visit, I can't increase the dose, they use weight based Copegus.  My last hemoglobin was 11.7 and the one prior to that was 11.5, but it's never really gotten super low, like one would think it should be?  I'm going to try not to read too much into this.  Susan400

[joemc34606]

My 4 week test was und and all my levels are good, my hgb is twelve right now. I'm sure there is some merit to that about absorption but I'm living proof you can clear and not be anemic. Yet anyway, long way to go. Joe

[flcyclist]

Susan,
I asked a similar question recently with the same concern.  My Hgb hasn't gone below 12 and I was concerned about Riba absorption and ultimately SVR.  I do eat some fat with each meal to increase absorption, but don't actually count fat grams since I'm on SOC.  I do wish there was a standard procedure for measuring riba concentrations rather than trying to base this on Hgb levels.

I think the more important question is - were you und at 4 weeks?  If so, I've been told that und trumps Hgb.  I've thought maybe increasing the Riba to push down my Hgb, but I'm already und at 4 and 12 weeks, so what benefit would I gain with the additonal risk of sides?    I'm not sure if exercising is helping my Hgb stay up.   On the other side, my ANC isn't behaving well, so need neupogen 2x/week.

[Bali05]

Ribavirin concentration in the later stages of 48 week pegylated interferon-α2b plus ribavirin therapy for chronic hepatitis C is useful for predicting virological response.

Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
*Corresponding author. Tel: [phone]; Fax: [phone]; E-mail: ***@****-u.ac.jp
Received September 14, 2010.
Accepted January 23, 2011.

Abstract
Objectives The current standard of care for chronic hepatitis C patients is a pegylated interferon-α plus ribavirin combination treatment. This study was carried out to determine the relationship between ribavirin concentration in the later stages of treatment and virological relapse.
Patients and methods Serum ribavirin concentration of 183 chronic hepatitis C patients (genotype 1) treated with pegylated interferon-α2b plus ribavirin for 48 weeks was prospectively measured by HPLC at weeks 4, 12, 24, 36 and 48. Patients with undetectable serum hepatitis C virus (HCV) RNA 24 weeks after the end of treatment were designated as having sustained virological response (SVR). Patients with undetectable HCV RNA during the treatment but with virological relapse after the end of treatment were designated relapse.

Results
The mean ribavirin concentration at each testing point of patients with SVR (1401, 1725, 1803, 1811 and 1901 ng/mL) was significantly higher than that of relapse patients (998, 704, 607, 643 and 654 ng/mL) at weeks 4, 12, 24, 36 and 48, respectively (all P < 0.001). Multivariate regression analysis for relapse extracted ribavirin concentration at week 36, but not cumulative ribavirin dosage. The cut-off value by receiver operating curve analysis for predicting a relapse was 1503 and 1562 ng/mL at weeks 36 and 48, respectively.

Conclusions
Ribavirin concentration in the later stages of treatment is an important marker of viral relapse.

http://jac.oxfordjournals.org/content/early/2011/02/22/jac.dkr034

[hrsepwrguy]

This is a very interesting question, I am in a trial that will be comparing ribavirin dosing, weight based compared to concentration controlled based on AUC 0-12 after first dose.

http://clinicaltrials.gov/ct2/show/NCT01097395?term=hepatitis+c+AND+colorado&rank=1

Primary Outcome Measures:
•ribavirin AUC-12 variability [ Time Frame: steady state (~weeks 9-10) ] [ Designated as safety issue: No ]
Demonstrate that concentration-controlled ribavirin dosing can achieve a targeted level of plasma exposure with reduced variability in the steady-state area-under-the-concentration-time curve (AUC0-12) compared with standard weight-based ribavirin dosing



Secondary Outcome Measures:
•safety - absolute hemoglobin declines [ Time Frame: end of treatment ] [ Designated as safety issue: Yes ]

•efficacy - early and sustained virologic response [ Time Frame: EVR (12 weeks) and SVR (24 wks after cessation of treatment) ] [ Designated as safety issue: No ]
Compare proportions with EVR and SVR in standard weight-based vs. concentration-guided ribavirin dosing groups

I start tommorow morning, arms will be decided in week 2, I will keep everyone interested posted on my numbers as much as possible.

Keith

[willbb]

dointime &Bali..I also agree ,,,my HGB. never really dropped...I even kept jacking up the Riba    1200 then 1400  still no drop in HGB..actually went up a bit on 1400???? it was like a big guessing game   and in the end still DET... so was there corelation...who knows

Best
Will

[dointime]

Bali05 - absolutely agree!  I'm so sick of 2nd guessing on this one.  I'll never know if my riba serum levels were too low when I did tx, never mind what the cause might have been.  And I was doing 1200mg a day.

Susan - it's a sure way to make yourself crazy trying to speculate on this subject.  I sure understand your frustration.  And I think it is disgraceful that you have been kept hanging on about your IL28B test.  That would really get my goat too.  Perhaps you could be polite but persistent in asking for your results.  After all, why should you be the only one aggravated by this.

All the best
dointime          

[evangelin]

Susan,
Maybe Wheaties is the cure for hemolytic anemia!      :>)  :>)  :>)  
Ev

[Bali05]

Hi Susan,

In order to maintain my regular diet on tx I took Riba dosages separate from my main
meals with a fat containing snack (avocado , buttered toast ect....)
Anemia is a toxic side effect of Riba. Not everyone experiences the same level of toxicity
and this reaction can also flacuate a little. It does not nessecarily proof that your Riba serum concentration is too low.
This issue has come up sooooo many times and I just don`t get why there is no Riba serum test
available to us.Many have tried to look for it .


b

[beeblessed]

Hi Susan.  What an interesting question.  I haven't a clue but hope more folks chime in.  As for the food aspect, I found this:

ADJUST DOSING INTERVAL: Food enhances the oral absorption and bioavailability of ribavirin. Administration of a single oral dose of ribavirin following a high-fat meal delayed absorption (Tmax was doubled) but increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) by up to 70% compared to administration in the fasting state.

MANAGEMENT: To ensure maximal oral absorption, ribavirin should be administered with or immediately after a meal.

As for the Anemia, this article is WAY over my head but may provide some answers for you.  It's a really long URL, but just copy and paste it into your browser to view the article:

http://webcache.googleusercontent.com/search?q=cache:FhsWRqVtAA8J:www.clinicaloptions.com/Hepatitis/Journal%2520Options/Collections/2010%2520JO%2520Hepatitis%2520Volume%25204/Articles/Thompson-Gastroenterol-2010/Commentary.aspx+does+anemia+hinder+ribavirin&cd=8&hl=en&ct=clnk&gl=us&source=www.google.com

[susan400]

Well, it's sort of a catch-22, I need a certain amount of fiber in order to keep things moving along-if you get my drift w/o going into T.M.I.   I don't really over do the fiber though (at least I don't think that I do, maybe?).  I've just about grown up my entire life eating whole wheat bread and I can hardly stomach eating a sandwich on white bread.  I do occasionally eat a roll that is white bread, or like a pizza dough that is white bread.  But, even when I've gotten a sub, I always order it on a whole wheat bun. But, I don't really eat that many things like high fiber cereal (because I think it's gross), or dried beans (because I don't care for them), so that's fiber that I'm not doing.  Like my sister loves Kashi cereal, and occasionally eats Fiber 1, not me, I prefer Wheaties.  But, I don't eat the cereal every day, so it's not hindering my Riba on a daily basis.    The only thing I think I might be doing it is maybe I'm not eating enough fat w/my Riba.  But, heck, it sure seems like I am when I'm eating more fat than I was prior to TX.  This whole TX formula is so incredibly frustrating because I've done this cr*p so many times and I still can't figure out what the heck I'm doing wrong.  I am still waiting for my IL28B test to get back and it's making me aggravated that it's taking so long.  But, since it's the trial that paying for it, I really don't have too much ability to complain too loudly.  Susan400

[dointime]

My understanding is that hgb is used as an indirect indication of the concentration of riba in the blood, ie. how well the riba is being absorbed, because it is hard to measure that concentration directly.  

So I guess the question would be - have you changed anything that might hinder your riba absorption?

When I was on tx my hgb never went very far down and I had 2 breakthroughs.  So I've racked my brains on if my diet was hindering my riba absorption.  The only thing I could find was that a high fibre diet might do that.  So if I ever do riba again I might throw out my wholefood muesli and bread and get the white stuff in along with cornflakes.  I am so looking forward to that - not.  

dointime