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.

[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.

[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.

[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.

[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

[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

[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....;^)

[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

[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

[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]

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

[Trinity4]

I agree with you rindaa.  Indicators are not exacts and because one is prescribed Procrit doesn't mean they will SVR.  If you don't need Procrit, you don't need it.  RVR trumps all and it is more common now for doctors to prescribe weight based riba for geno 2 & 3 but it looks like your husband had the coveted RVR regardless of his genotype.  His chances at SVR have been dramatically increased.

Good Luck
Trinity

[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

[choprchk]

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

[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

[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]

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

[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

[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

[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.

[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.

[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.

[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.

[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.

[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