Your "Great" labs might mean the opposite of what you think they do.

[jmjm530]

Always killed me when people here report that my doctor said "my labs look 'great"" or that "my hemoglobin is great" -- when in fact an association between anemia and riba absorption has been known for some time. Now, we have the logical association between anemia/riba absorption and SVR. Bottom line IMO  is that having little or no anemia should at least signal a discussion with your doc about increasing your riba dose, regardless if it's weight based. Espeically if your viral decline isn't what it should be. Also note Procrit's role in keeping people on tx with their anemia. Thanks to "CoWriter" for bringing this particular presentation to my attention.
------------------

Oral Presentations
http://www.kenes.com/easl2009/Orals/276.htm

Session Title: Parallel Session 15: HEPATITIS C VIRUS NATURAL HISTORY AND THERAPY
Presentation Date: Apr 25, 2009

HEMOGLOBIN DECLINE IS ASSOCIATED WITH SVR AMONG HCV GENOTYPE 1-INFECTED PERSONS TREATED WITH PEGINTERFERON (PEG)/RIBAVIRIN (RBV): ANALYSIS FROM THE IDEAL STUDY

M. Sulkowski1, M. Shiffman2, N. Afdhal3, R. Reddy4, J. McCone5, W. Lee6, S. Herrine7, S. Harrison8, W. Deng9, C. Brass9, K. Koury9, S. Noviello9, J. Albrecht9, J. McHutchison10
1Johns Hopkins University School of Medicine, Baltimore, MD, 2Virginia Commonwealth University Medical Centeru, Richmond, VA, 3Beth Israel Deaconess Liver Center, Boston, MA, 4University of Pennsylvania Health System, Philadelphia, PA, 5McCone Endoscopy Center, Alexandria, VA, 6Clinical Center for Liver Diseases, Dallas, TX, 7Thomas Jefferson University, Philadelphia, PA, 8Brooke Army Medical Center, Fort Sam Houston, TX, 9Schering-Plough Research Institute, Kenilworth, NJ, 10Duke Clinical Research Institute, Durham, NC, USA

Background and aims:
Peginterferon (Peg)/ribavirin (RBV) causes significant hemoglobin (Hb) decline leading to side effects and RBV reduction in ~30% of patients (pts). The effect of Hb loss on sustained viral response (SVR) is unknown.

Methods:
3070 HCV genotype-infected pts were treated for 48 weeks with Peg2b 1.5 or 1.0mcg/kg/wk + RBV 800-1400mg/day, or Peg2a 180mcg/wk + RBV 1000-1200mg/day. Anemia was defined as Hb 3 g/dL, 43.7% (984/2250); ≤3 g/dL, 29.9% (231/773) (P8 weeks):
Anemia/no EPO, 59.3% (162/273);
Anemia/EPO, 55.0% (116/211); P=0.33.
Among anemic pts, EPO was associated with less early (< 0.001).

Conclusions:
Among HCV genotype 1-infected pts treated with Peg/RBV, the magnitude of Hb decline is strongly associated with the likelihood of SVR.
The effect of EPO varied by time to anemia;
no benefit was observed for pts who became anemic after treatment week 8.
These data suggest that Hb decline may be a pharmacodynamic marker of treatment effectiveness and that the primary effect of EPO was to prevent treatment discontinuation in pts with early anemia.

[jmjm530]

Not a big jump to speculate that those genotype 1's with little or no side effects after a few weeks may not be absorbing enough ribavirin and therefore may have less of a chance of SVR. Of course there are exceptions, as we all react differently to anemia, but at a minium someone with little or no side effects should be xtra vigilant about having their hemoglobin checked and if little or no drop from pre-treatment baseline, then discuss with medical team about increasing ribavirin.

[Upbeat]

Thanks jmjm
                    It seems to me that there are a lot of factors at play in determining your chance of SVR.  For some reason the medical community sees this as a one size fits all.  With all the info avaiabile it would seem a persons odds of SVR should be known quite early in the treatment and should stop the treatment when indicators point to a bad outcome.  Humm a little common since would go a long way.
                                                                                                     Ron

[jmjm530]

it would seem a persons odds of SVR should be known quite early in the treatment and should stop the treatment when indicators point to a bad outcome.
-------
Yes, but conversely some markers (like lack of hemoglobin decline) can also be used to tweak treatment if hemoglobin is monitored weekly and compared to baseline. Little or no decline, then up the ribavirin, as opposed to telling the patient "your labs look great". Duh.

Also, if a patient has a prior track record with treatment, then the old records can be examined to see what the hemoglobin reaction was the first time. In this case, if not a sufficient decline the first time, then a higher initial dose of ribavirin should be considered.

Moving along to the more speculative -- and in cases where a more aggressive approach is desired for any number of reasons -- we go into the area starting tx  using higher than weight-base dosing as well as pre-dosing ribavirin prior to treatment so that the serum riba levels are up there by the first injection. And based on what we know, you might consider pre-dosing ribavirin until you have at least a two-point drop from pre-tx baseline, i.e until you are anemic. To boost serum ribavirin levels even more, one might consider the use of Procrit (epo) at some early point or even prophalactively.

This paper btw seems very consistent with other similar studies, including those that show serum riba levels (via HPLC testing) help deterimine both RVR and SVR. Unfortunately HPLC testing for serum riba levels is not available except in trial situations, but if it were, then one could reasonably pre-dose and  keep increasing the riba  dose until a set serum riba level was met. At that point, Procrit (epo) could be administered if needed per symptons, and only then would the first Peg injection start.

-- Jim

[jmjm530]

Look at the serum riba studies via HPLC testing showing RVR and SVR associated with higher serum riba levels. To me, this is the same thing just put another way as in general more ribavirin equals more anemia equals higher serum riba levels equals higher rvr and svr. BTW this is more specific to geno 1's because riba seems to play a more important role in geno 1s

[jmjm530]

Nygirl double dosed riba from day one.
-----------------------------
Could be wrong, but I don't think she double-dosed at all and certainly not from day 1. My recollection is that she started either normal or sub-normal dosing and then boosted the dose after tx began. BUT even if she did double-dose, and I'm pretty sure she didn't -- people metabolize riba quite differently and that is the problem with weight-based dosing. Conceivably a person who double-doses could effectively have a lower serum riba level than someone who single-doses due to a number of factors including kidney clearance per some of the early LIndahl studies.

Trinity: So you're saying someone like myself, who should only be taking 800 mg of riba but taking 1000mg should bump up to 1200 or 1400?  
----------
Not at all. If you're a geno 1 and 800 mg gives you let's say a two point drop of hgb from baseline in a few weeks then its probably enough. Conversly if you took 1400 mg and your hgb curve remained flat after 4 weeks then 1400 might not have been enough. Should add that while hgb drop is adding up to be a very important indicator, it's still a bit crude compared to the actual serum riba levels which unfortunately cannot be measured because of lack of HPLC testing.

From what I've read for well over a year, there are plenty of folks who EVR and SVR on weight based riba dosages and never go anemic.
----------
Some? A few? Plenty? Are thesse geno 1's? That's the problem with anecdotals :) Regardless, the role of riba and riba absorption is too important not to factor into an individualized tx plan. Since HPLC testing doesn't exist, then hgb drop (anemia) is all we can go by.

[jmjm530]

The other point not be be missed is that RVR probably trumps anemia as a predictor even though anemia is associated with RVR and now SVR. So in other words, if someone is RVR (but not anemic) , then I'm guessing that there chances of SVR are similar to someone who is RVR and anemic.

[jmjm530]

I believe her entry is consistent which what I said and not that she double-dosed from the beginning or even ever double-dosed at all. Hopefully she will clarify on MOnday

[epiphiny]

I tend to agree with Jim on this one, based on my personal experience.  On my first tx I was dosed at the standard 800mg Rib (Geno 3) and I felt little side effects and my Hb always stayed in a good healthy range.  At no stage did I ever achieve UND in my 24 weeks of treatment.

This time round I have been on 1200 Riba (weight based) and have become anemic 3 times.  The first time was at week  4 or 5 when dose reduction. This also coincided with becoming UND so that shows me a direct relationship to the efficacy of riba, anemia and outcome.

Each time my bloods have reached up over 10 I have asked to go back up full dose as I really believe it is about the correct riba dosage per individual and the anemia levels are the only way we have here in NZ to gauge response to tx, other than VL testing and LFTs, but LFTs can swing so.....

I also tend to agree that not everyone metabolizes the Riba in the same way and therefore different people have different responses to the same amounts even if they are about the same weight.  I have read of a member here who is a small female and was on massive doses of riba whose body metabolized it so fast that it never got a chance to work, she is simply 'immune' to riba, if you will.

[newleaf09]

The whole thing is very Judeo-Christian.  You must suffer to get to heaven (SVR n this case).

I do hope everyone was informed of taking food with the riba to slow it's absorption and keep it circulating in the blood longer.

[jmjm530]

The whole thing is very Judeo-Christian.  You must suffer to get to heaven
---------
LOL. Yes, unfortunately that is true in many cases because anemia is not fun.

As to the riba, taking the riba along  with a meal with a decent amount of fat does increase the bioavailbility of ribavirin, meaning that more is accessible to the system.

[mikesimon]

I have believed for quite a while that, in the absence of plasma level testing for ribavirin concentration, hemoglobin drop is the best indication that one is adequately dosed. In fact, we've had this discussion before and I thought the general consensus was that anemia is an indication that we're not under-dosed and that SVR is more likely. I have seen the experts suggest this - perhaps the same ones cited above so I always accepted the premise. I know that Jim has always thought this too.
My experience with multiple treatments seems to corroborate this.
You gotta love a little anemia.
Mike

[portann]

From study posted above:

"no benefit was observed for pts who became anemic after treatment week 8."

"Anemia was defined as Hb 3 g/dL, 43.7% (984/2250); ≤3 g/dL, 29.9% (231/773) (P8 weeks).."

I don't understand that second line. What is the study's definition of anemia and what does "3 g/dL" mean in the language of my lab reports.

[mikesimon]

3 grams per deciliter.

[apache1]

Well, will play the devils advocate here

While this conclusion is probably correct for geno 1, not sure geno2, or maybe even geno3, need to get to the level of Anemia that geno 1 needs for the best chance at svr.

Also does the damage riba does to ones red blood cell producing marrow ever come back to pre tx  levels ?... mine hasn't yet.

HGB was 16.7 before tx, now 4 months post eot (und@12wk post) hgb hovers around 15.
My endurance levels and stamina when running and exercising is not back to pre tx levels yet. I am wondering if it ever will be, and if the hgb killing riba had anything to do with it.

Even though the highest riba levels are associated with the best svr rates... be carefull promoting high dosage riba. My Dr uses procrit, but does so with caution. NP says its a nasty drug.
I know we all want to get a SVR status, but our Dr's are the best ones to make the decisions of what we should or have to tolerate in order to get there.

All I am saying is be very careful with High Riba dosing and Anemia. Dangerously low HGB levels can occur.  For someone with stage 0-1 liver disease, and a weak cardio-vascular system, this can't add years of life, and might not be the best compromise...

IMO your Dr should be the one to determine proper riba dose. If you pressure him to up your dose because of studies like the above one,
and you have adverse advents (that might take you off tx or dose reduce) your Dr might not be 100% responsible, and you have no one to blame but yourself.

That being said, I know some of us can, and have, tolerated very high ifn and riba dosage.
All the power to them, and it will probably help them reach SVR.
I just would hate to see the 105lb elderly lady self-increase her dose because of a study like this, along with her less than desired hgb drop, then suffer an adverse advent.

jmho,
apache

[apache1]

correction
suppose to be adverse event,,, not advent...lol

[jdwithhcv]

"...anemia is not fun."

Jim, how can you say such a thing?  Not fun to huff and puff and gasp for air?  Not fun to have your vision go out and suddenly hit the floor like a sack of grain?  Why, its the best way I know (short of arson) to fill your house with cute firefighters!

I got slammed with anemia early, but then I also got RVR.  Could never get my hgb much above 10 so I took procrit for the duration!  I did not want to dose reduce and found the tradeoff was worthwhile for me.

jd

[jmjm530]

Apache: While this conclusion is probably correct for geno 1, not sure geno2, or maybe even geno3, need to get to the level of Anemia that geno 1 needs for the best chance at svr.
--------------
This is correct. The study was for geno 1's and as far as I know the previous studies on serum riba levels via HPLC testing was also for geno 1's. This does of course not mean there is no relevancy for geno 2's and 3's, just perhaps less.

JD:  "...anemia is not fun."
Jim, how can you say such a thing?  Why, its the best way I know (short of arson) to fill your house with cute firefighters!
----------------------------------------------------
Well, I guess if some cute female firefighters showed up at the house I might revise my opinion :)

-- Jim

[Marcia2202]

I think that there sometime is a misinterpretation of anemia on the board. Not being below 10 doesn't mean one does not have anemia.

I have sometimes myself stated that my blood work is looking good, meaning that it looks good for being on treatment, meaning that I didn't need Procrit, yet. An Hgb of 10.5 is low, anything under 12 is considered low.

Even though I was anemic all the way through tx, I still did not clear at 4 weeks.

Marcia

[jmjm530]

Marcia: Not being below 10 doesn't mean one does not have anemia.
----------------------

To quote from the paper, "the magnitude of Hb decline is strongly associated with the likelihood of SVR. "

So, it's not the absolute number per say, or even the technical definition of "anemia", but how much of a decline from pre-tx baseline that is the main thing. Makes sense since many of us start at much different pre-tx hemoglobin levels.

[jdwithhcv]

Marcia makes a good point.

hgb < 13.2 indicates anemia

hgb < 10 is the criterion for procrit (epogen)

Many people become anemic on tx, however most doctors will not prescribe (nor insurance companies approve payment for) procrit untli hgb drops below 10.  As hgb levels rise, many doctors will discontinue procrit because it carries a risk of blood clots.

[HCA]

Another useful marker is creatinine.Patients with anemia and rising creatinine are retaining ribavirin and can tolerate dose reduction without prejudicing SVR.
People are gradually learning that ribavirin plays no part in in viral suppression but a major part in preventing relapse (and break-through).High levels of ribavirin are necessary at the point that viral suppression takes place in order to compromise the design of a  successful variant .
A drop in Hgb is indeed a good sign.

[jmjm530]

Interesting you mention creatine, because Lindahl and CO used a pharmakinetic formula for initial riba dosing (as opposed to weight based dosing) involving kidney function markers such as creatine in their 2005 small landmark pilot study on high dose ribavirin. From what I've been told the formula used underestimated the amount of riba needed and therefore it had to be bumped up based on HPLC testing. But the concept does hold and therefore people with impaired kidney function (dialysis patients for example) can do quite well on treatment with much lower doses of ribavirin although I'm unaware of any exacting formulas in this regard other than anemia, unless of course HPLC testing is available in trial setting.

[portann]

Okay, I don't mind if you freak me out! :)

I started tx at 15 and at eight weeks was 12, which is not officially anemic. So? Say it straight, I can take it....

I'm taking (was taking!) 17.8 mg per kilo of riba, so could I have really taken more, given that I am, after all, an elderly lady?

In hindsight, should I have stopped tx at eight weeks, calculated that SOC wouldn't do it for me and waited for the PI's?

My 'true' anemia didn't hit for another month, which is past the study's significant point.

[apache1]

Good article and discussion Jim, thanks for posting.

My creatinine levels shot high during tx and now kind of getting back to normal levels...but not there yet.

Wonder the significance of that creatinine increase, and if riba damaged my kidneys? They were well within normal levels before tx.

hgb dropped from 16.7 to 14.8 during tx

apache

[jmjm530]

For the umphhh time LOL it's not the number but the DROP. You dropped 3 points. That's a sizeable drop. You're good to go. You will SVR. Guaranteed!

-- Jim

[jmjm530]

Just so you know, almost everyone is convinced they will relapse after treatment for one reason or another. Human nature I guess. So any insecurities at this point are entirely normal but  will have no effect on the virus  which I'm sure is long gone by now :)

--Jim

[rindaaa]

I am new to all this...my husband was the one dx with hep-c and is currently being treated.   My husband  has had no interest in researching and learning all he can about this dreaded disease so I have started learning what I can for him.

I have since found out he is on a "low" dose of Riba for someone his weight which concerned me since he genotype 1a with early cirrohosis.  When he started trt he weighed 222 lbs.  His GI only has him taking 800 mg of Riba per day.  (That concerned me big time!)  I was on another board and they told me my husband should ask the doctor WHY such a low dose?  My husband says his doctor knows what he's doing so he isn't worried about it.   :o

All that being said...he just say his GI to get results of his 4 week VL and counts.  And in "his" case it seems to be working fine...meaning the lower dose.  He is already undectable.  And since its such a low dose of Riba he hasn't needed any neulasta or Procrit.  Which Procrit is really NASTY stuff.  (I know because I went through cancer treatment for a year and it wasn't till later all the bad news came out about how dangerous Procrit can be.)  So if you can get away with NOT having Procrit...thats the way to go.

So I don't think in all cases it's true that if you don't see your counts drop to where you need procrit and neulasta then the riba is not working.  (So far this small dose is working great for my husband)  But as we know every "body" is different.   (This is an interesting thread)

Rinda

[jmjm530]

When he started trt he weighed 222 lbs.  His GI only has him taking 800 mg of Riba per day.  (That concerned me big time!)  I was on another board and they told me my husband should ask the doctor WHY such a low dose?  My husband says his doctor knows what he's doing so he isn't worried about it.
--------------
The person on the other board has a VERY good point. I'd certainly want to know why he's only on 800mg/day of ribavirin when weight-based dose is closer to 1400/day.  You say he is undetectable. Do you know exactly what week he was undetectable and what test was used? If you don't, ask the doctor for copies of ALL bloodwork from pre-treatment to now. Honestly, many GI's know less about treating Hep C than many folks here but hopefully your husband's GI is the exception exeept your post honestly has me wondering. As to Procrit, many here take it and I can say that the consensus is that it has the least amount of side effects of any of the drugs we take on treatment.

If you really want to learn about this disease and treatment, I'd first start by collecting all your husband's records to see what is actually going on, after all I'm sure his treatment is your first concern.

-- Jim

[choprchk]

This is definitely the best discussion I've seen!!!  

[Willy50]

I would agree with Jim.  I wondered if your husband might be a genotype 2, which could explain the lower dose but no, it appears that he is a genotype 1;

http://www.medhelp.org/posts/Hepatitis-C/Working-while-on-treatment--food/show/780616?personal_page_id=432090&;post_id=post_4068591

All I can say is that full dose riba is associated with more durable response.  Just because he is clear doesn't mean that he cannot break through or rebound.

The fact that he RVR'ed is a very good sign but of course one would assume that he would have also RVR'ed and sooner with a higher dose.  At some point when one reduces the riba too far you will start to see problems with clearing, breaking through, or rebounding.  It is sometimes hard to know where that tipping point is for everybody and so one follows dosing protocols  A few people here might theorize that one might even "surge" a little in the beginning with if anything a bit more riba.  Ribavirin is probably is most important at the beginning of TX and less so at the end of treatment.

Perhaps your doctor is aware of something not apparent to us.  In any case the the RVR is a very good sign.  It also speaks well that the doctor would check at 4 weeks.  I still wonder if the riba dosing could end up being crucial in his case.

best,
Willy

[Rockerforlife]

Bsaeline HGB  15.3
WK 2               12.3
WK 4                11.7
WK 6                 11.9
WK 8                  12.6
WK 10                12.3
WK 12                 10.8
WK 16                   12.3
WK20                     11.8


UN after 2 weekS on Boceprevir

12OO mg RIBA dose

[jmjm530]

Very nice Rock. Very nice. BTW do you have those say hgb numbers for your first treatment that failed? That might be interesting.

-- Jim

[Rockerforlife]

First TX IN 2006

Basline HGB   15.0
WK 2             12.2
WK 4             12.0
WK  6             11.8
WK 8              11.6
WK 12             11.6
WK  18             11.5

ALL TRU TX    average 11.0

1200 RIBA dose....UN sometime after wk 12

SOC drugs only

[Rockerforlife]

notice at wk 12 in my second TX...10.8 HGB....this was the just after starting the boceprevir...i myself dont think SVR depends on the change in HGB

[Proactive]

Pre tx hgb 1/23/06  18.0; 10/5/06 17.0
baseline hgb 10/26/06 17.4  (1200 mg riba)
wk 1    16.6
wk 2    16.4
wk 3    14.9  start of hgb rebound
wk 4    15.3
wk 5    16.5
wk 9    16.2  Increased riba to 1400 mg
wk 13  14.7  increased riba to 1600 mg (weighed 175.9 lbs)
wk 18  14.0  Finally undetectable
wk 22  14.6
wk 26  14.0
wk 30  13.4
wk 36  12.9
wk 41  12.0
wk 46  11.2
wk 52  11.2
wk 53  11.1
wk 53  11.1
wk 56  11.9
wk 60  12
wk 67  12
about 12 through wk 72

As you can see, I was riba resistant (vbg), a late responder and far to anal to be keeping all this info!
SVR
pro....;^)

[Willy50]

I wouldn't want to try to define what this thread is doing but when one adds a drug like Boceprevir, Telaprevir or any of the new anti-virals I think you may be comparing apples to oranges.  I'm guessing that this discussion only pertained to SOC and not to the new PI's, for instance.  Even even limiting the discussion to current SOC there seems to be some cause to wonder if things are directly related.  There will always be exceptions.

The Headline of the study Jim posted was;

"HEMOGLOBIN DECLINE IS ASSOCIATED WITH SVR AMONG HCV GENOTYPE 1-INFECTED PERSONS TREATED WITH PEGINTERFERON (PEG)/RIBAVIRIN (RBV): ANALYSIS FROM THE IDEAL STUDY "

"Associated" being the key word.

best,
Willy

[jmjm530]

Willy: I wouldn't want to try to define what this thread is doing but when one adds a drug like Boceprevir, Telaprevir or any of the new anti-virals I think you may be comparing apples to oranges.
--------------------------------

You are correct. This study refers to geno 1's on SOC and that's why I asked Rocker what his hgb values looked like on his first failed treatment as he was a geno 1 on SOC. That would be apples and apples comparing his response to the study:)

Willy:
"Associated" being the key word.
----------
No, actually the key words are *strongly associated* per the abstract conclusion as titles are simply that and often not written by the docs. From the abstract:

Among HCV genotype 1-infected pts treated with Peg/RBV, the magnitude of Hb decline is strongly associated with the likelihood of SVR."

------------
To me, this is very compelling although frankly I needed little convincing since this study is not in isolation and a number before it have shown a direct association between anemia and serum riba levels with RVR. This is just a logical outcome of that concept as I see it and a very useful tool in tailoring treatments in treatments.

-- Jim

[Proactive]

and I'd like to add, while I didn't have one of the top doc's sometimes listed here, I was very fortunate to have a doc that clearly thought outside the box and advocated hit it hard..I would recommend Dartmouth to anyone for tx.

[nygirl7]

Yup I was taking from 1200 - 1600 at any given time instead of the 800 tops I should have been. It wasn't until Dr. J freaked out that I dropped down but it varied on how many I felt like taking.

I don't remember which Mondays or Tuesdays I took 1200 or 800 (well that was after week 46 I think) or 1600 though. I'm not anal enough to keep a diary but at five feet seven inches tall (after losing 20 pounds) and about 100 pounds - maybe it is a slight exageration but I consider that double dosing the riba.

Point is did it help me to lose six full points at week 2/3? I'll never know but I tend to agree that Dr. J might have been right and a body can only absorb what it can absorb and the rest is a moot point. Without the Procrit though - I would have NEVER made it past week 3.

If I had to do it now (although I am much fatter than I was after gaining an extra bit) I probably would stick to 1000 and just let it go. - but I'm kind of crazy and I just might start doubling when I felt like it because I got nervous again.

Still................had to do the 72 weeks and I believe that was my personal key to success but I will never ever know.

[nygirl7]

Oh important factoid - I did drop down to viral load to 411 at week 4 -------- but then it took another 12 (???) weeks after that even on being what I personal consider max riba for me (and the hemo drop) then flatline.........zzzzzzzzzzz..............so

Is it the initial hit that does it?

I don't know but for me it didn't seem to matter after that 4 week (where we are supposed to get to RVR) that the extra riba mattered.