Avatar universal

Some clarification if someone knows or doctor has explained

It is a known fact that HCV therapy(specifically INF. can reduce neutrophil counts (neutropenia) in patients quite often.
However it seems clear from the thousands that have been involved in the studies below that there seems to be" little" if "none" at all correlation between low neuts(ANC) and increased incidence of infection.
The labeling on INF. is to reduce it if there is incidence of  neutropenia ,however I can fully understand doctors not wanting to do that ,especially early ,and not jeopardize possible treatment success,however I fail to fully grasp why some doctors are very quick to prescribe  another fairly powerful drug like Neupogen (which I don"t believe is FDA approved for HCV therapy) that often can have  side effects of it"s own(we have often heard of deep bone pain,amongst some other ones listed) when the studies below show  such results.

I know my own Hepa says he rarely prescribes Neup   unless the ANC was extremely low combined with the patient having other health factors,specifically diabetes (which may increase chance of infection )

Possibly I have missed something ,on why some doctors are often  prescibe this   and if any one"s doctor has explained why they are quick to add this to the soup I would appreciate the info. Possibly it is the diabetes??


119 patients in this study: No incidence of infection because of low neuts


In this study 4243 patients:


Two recent reports indicate that there is no association between neutropenia in this population and the development of bacterial infections.[35,36] In the largest study report, featuring preliminary data from a still ongoing multicentre trial, there were only 30 of 4243 patients (0.7%) who developed severe infections during anti-viral therapy.[36] When examined closer, the mean ANC nadir in this group was no different than that of the entire treated study population. There was also no difference in the percentage of patients who had ANC < 750/mm3, or was there any association between the ANC nadir and the development of infection. These data suggest that further meticulous studies are required to determine the criteria for dose reduction and to define the use of G-CSF for PEG-IFN-induced neutropenia.

In this study 2876 patients:


Bacterial infections during treatment with peginterferon alfa and ribavirin are not associated with neutropenia. Older patients and patients with poorly controlled diabetes mellitus have a greater risk of developing infections during HCV treatment.


In this study 319 patients:


During the treatment with pegylated interferons and ribavirin, we did not find a correlation between neutropenia and infections. This result provides a support for the notion that current guidelines for pegylated interferons dose reduction in the treatment of chronic hepatitis C for hematologic toxicity could be overly strict.

28 Responses
148588 tn?1465778809

It's my understanding that with neutropenia you're not more *prone* to infection, but once infected (celitis,bronchitis, pneumonia, whatever) it's more diffucult to *get rid of* the infection. Antibiotics become ineffective because they have nothing to work with. My understanding only. Hopefully someone has a better one.
Avatar universal
Hi desrt...CYA was my first thought on it,as INF was labeled that dose reduction was the protocol so they  CYA on absolutely anyone even if only 1 of every 800 got an infection and couldn't fight it (as the studies show) ,then the docs follow along ,just in case they happen to have the one patient in 800 that gets a bacterial and dies...

Seems plausible given the roughly 8000 people they looked at with very few problems..

163305 tn?1333668571
I'm glad you posted this and hope someone can give a good answer.
I hate the stuff, not for any reason other than it feels 'wrong.'

I've gone to the clinic, taking public transportation, and come home only to get a phone call from the nurse telling me to take neupogen because of my low anc.

When I saw my hepatologist and asked why I have to take it when my anc drop  below750, he explained some theory about infections and post-transplant patients, how it hasn't been proven in research or his experience.
He said it was what they do there.
He'd agreed let me go down to 500 as long as I don't hold him responsible if I get an infection.
The point is, it's the protocol at that clinic.

Unfortunately, a lot of medical care comes down to, 'this is how we do it."
Doesn't mean it makes sense. Look at how many of us needlessly had our tonsils removed.

1669790 tn?1333662595
Will, I've had a low ANC throughout trt and have been on 2x per week trt since week 8, now at week 37.  In my situation my GI referred me to the Hematologist for addressing the ANC once it went below 500 - it was actually down to about 350.  He wanted to do this rather than a dose reduction of Inf.  

The Hematologist/Oncologist is associated with a cancer treatment center that treats a large number of cancer patients with chemo, radiation, etc.  As you would guess many are 65+, so the risk of infection from this aggressive trt is real.  Unforunately, the Hema doesn't trt many HCV patients and I believe this philosophy of being very conservative with keeping the ANC up is a spillover from trt cancer patients.   In my case I do think - CYA.

I've had this discussion with him and actually showed him a couple of the articles referenced, but he stood his ground and proceeded to tell me a few horror stories, what to do if I spike a fever, etc. to scare me a bit.  My ANC number on Mondays after the Friday eve Inf shot is usually around 100-300.  By Thursday the number rebounds to about 700+ with some variation from week to week.  I actually skipped last Thursday's visit/neup shot and have missed a few prior due to travel, appointments, etc.  

I agree with the published studies.  My current plan is to continue to do the Monday visit/shot to keep me out of trouble, but skip the 2nd visit/shot.  I've had a few Monday readings in the 100-200 range, so I'm a bit concerned about just stopping it.  Btw, I'm going to the hema's office for the shot, rather than do it at home since it works out better for insurance purposes.  Plus I get to see the cbc's each week.  

So to summarize my ramblings, I think some of this is a spillover from Hematologists/GI's/Hepa's that aren't keeping up with current literature and default to standard protocols since they are either unaware or just want to CYA.
446474 tn?1446347682
Hi WIll.

My 2 cents related to your comment..."I know my own Hepa says he rarely prescribes Neup unless the ANC was extremely low combined with the patient having other health factors,specifically diabetes (which may increase chance of infection) "

When I did treatment in 2008 (I was still compensated) I was given Cipro before stating treatment and throughout as a prophylactic against infection for the reason your doctor mentioned. Cirrhotics are more prone to infection then the general population and Cipro is an antibiotic that can be taken for many months to prevent infection. This was and as far as I know still standard procedure for treating pre-transplant cirrhotics like myself at my transplant center.

I will get more details when I have time later. I think it is mentioned in a doctor update on state of the art treatment for cirrhotics video my hepatologist did about hepatitis C and cirrhosis for Gastroenterologists and Hepatologists.

Happy New Year!!!!
Avatar universal
Dsert,flcyclist,OH,and Hector:

Thank you for trying to help me understand this better.
Probably most of you know I try to site credible studies to back up most of what I give my opinions on here,however every time I was telling someone to talk to their doctor about possibly starting "Neup" when ANC got low ,I found I was doing it only because that is what people here were saying their doctors almost automatically did.
So I asked my own Hepa(actually I asked two in the large liver center and teaching facility I am treated in) and both of them said the same thing. They would only prescribe Neup if someone  had very low ANC from therapy "combined with possibly some other health issues (.specifically diabetes and yes Hector  my doctor also mentioned chirrotics ),I am sorry I failed to mention that  as it would certainly fall into special consideration.

That combined with all the studies done I could find ..(that I cited above ) it clearly seems Neup(a very powerful  drug with possible side effects may be very much over-prescribed  in The HCV treatment regime.. given the" risk vs. benefit  "consideration.
I always think it is best to listen to our doctors(if knowlegable and experinced about HCV)..however... when it comes to injecting  this powerful drug again given the overwhelming evidence in many large studies ,I hope it is not just    "this is how  we always do it" as  OH mentions..
Thx again folks...this one was bugging me a tad..

Happy New Year  to All   ;0)


It seems cyclist and desrt have brought up a good point ...this may be a CYA for the rest of  the patients treating that "do not" have diabetes or are chirrotic" because of  the  handful of thousands followed in studies that  got into problems. Cyclist says his doctor told him of the horror stories and what doctor wants HIS patient to be one of those stories.

orphanedhawk states that she hates the stuff and we have heard that on a number of occasions here and there is always the unknown about so many drugs about the long term sides.

I guess it was just bothering me about the benefit vs. risk of this drug   especialy when all of the studies I cited above (for people without chirrosis and diabetics) clearly the data shows infection and problems with such "is not"aproblem if neutrpoinia develops ,
419309 tn?1326503291
A few years back literature warned providers about continuing therapy in those with neutropenia; CYA or not, a doctor's oath is to do no harm, and the worse of all adverse events, death, makes the community sit up and take notice:

TITLE: Neutropenic enterocolitis: An unusual complication of HCV combination therapy with PEG-IFN and ribavirin.  
Author:  Kasturi, Krishna S.; Mummadi, Rajasekhara R.; Sood, Gagan K.; Add.Author / Editor:  Kasturi, Krishna S., et al
Citation:  European Journal of Internal Medicine Jul2008, Vol. 19 Issue 5, p372-373  
Year:  2008  
Abstract:  Abstract: Drug induced neutropenia as a consequence of intensive chemotherapy for hematological malignancies and solid tumors is known to be associated with severe, life-threatening infections such as neutropenic enterocolitis. However, the neutropenia associated with HCV combination therapy with Pegylated Interferon [PEG-IFN] and ribavirin is considered to be well tolerated in patients without other co-morbidities. We present a case of a severe gastrointestinal complication in a patient receiving HCV combination therapy and advocate caution in continuing therapy in patients with neutropenia, especially in the presence of underlying co-morbidities such as cirrhosis

"Fatal Neutropenic Enterocolitis during Pegylated Interferon and Ribavirin Combination Therapy for Chronic Hepatitis C Virus Infection"
Author:  Kim, JH  Add.Author / Editor:  Jang, JW; You, CR; You, SY; Jung, MK; Jung, JH  
Citation:  GUT AND LIVER 3 (3): 218-221 SEP 2009  
Year:  2009  
Abstract:  It is known that neutropenia caused by combination pegylated interferon plus ribavirin therapy for hepatitis C virus (HCV) infection is well tolerated and carries a negligible risk of infection. Neutropenic enterocolitis is encountered most frequently in patients with hemato-oncologic diseases who are undergoing intensive chemotherapy. However, little information exists regarding this life-threatening event in the setting of HCV therapy. We present here an unusual case of fatal neutropenic enterocolitis in a cirrhotic patient receiving combination therapy for HCV infection. This is the first report of a death from neutropenic enterocolitis associated with treatment for chronic HCV infection. The present case suggests that caution should be exercised when continuing HCV therapy in neutropenic patients with advanced fibrosis, and the decision to maintain such therapy should be balanced against the potential for serious adverse events. (Gut and Liver 2009;3:218-221)

IMHO, the above cautions, coupled with higher SVR-rates in the setting of growth factor use for hemotologic complications, provides reason for the medical community to continue administration even when risks are low:

" Granulocyte colony-stimulating factor for hepatitis C therapy-associated neutropenia: systematic review and economic evaluation. "
Author:  Tandon, P.; Doucette, K.; Fassbender, K.; Vandermeer, B.; Durec, T.; Dryden, D. M.; Add.Author / Editor:  Tandon, P., et al.
Citation:  Journal of Viral Hepatitis Jul2011, Vol. 18 Issue 7, pe381-e393  
Year:  2011  
Abstract:  Hepatitis C virus (HCV) treatment requires maximal adherence to pegylated interferon (Peg-IFN) and ribavirin to achieve a sustained virologic response (SVR). Neutropenia is the most common cause for Peg-IFN dose reduction. Our objectives were to evaluate the effectiveness, safety and cost-effectiveness of granulocyte colony-stimulating factor (G-CSF) versus Peg-IFN dose reduction for HCV therapy-associated neutropenia in treatment naive adults. We conducted a systematic review to identify controlled trials and observational studies. Study selection, quality assessment and data extraction were completed independently by two investigators. Cost-effectiveness and cost-utility analyses compared G-CSF with dose reduction. Nineteen studies were included. In one trial, the SVR for those receiving G-CSF was 54.5% (95% CI: 34.7-73.1) compared with 26.3% (95% CI: 11.8-48.8) for dose reduction. The remaining studies were case series or retrospective cohorts and provided weak evidence for the relationship between SVR and G-CSF. The risk of adverse events, including infection, associated with G-CSF was low (13.1%; 95% CI: 8.0-20.8) and clinically insignificant. G-CSF had an incremental cost-effectiveness ratio of $41 701 per SVR achieved in genotype 1, and $16 115 per SVR achieved in genotype 2 or 3. Estimates were robust under a variety of resource and intervention scenarios. While administration of G-CSF may enable patients to remain on or resume optimal HCV therapy, there was weak evidence that this improves the likelihood of SVR compared with dose reduction. Adverse effects of G-CSF are mild. The economic evaluation was inconclusive. [ABSTRACT FROM AUTHOR]nalyses compared G-CSF with dose reduction. Nineteen studies were included. In one trial, the SVR for those receiving G-CSF was 54.5% (95% CI: 34.7-73.1) compared with 26.3% (95% CI: 11.8-48.8) for dose reduction.  

With SVR being the goal, I think docs are cautious to steer off the course of "statistical data."
Avatar universal
Thx Eureka..we crossed  :0
408795 tn?1324935675
Neupogen is definitely approved by the fda but is mainly used for cancer or leukemia patients.  Maybe it just works better with the drugs used for those illnesses, idk.  

Avatar universal
In cancer patients it does seem fret it has an overwhelming  benefit vs. risk .... at least from  what the literature says and how much it seems to be used in that community... ..
Avatar universal
How's the weather down there??  


Avatar universal
I will let this one go cause its NEW YEARS !!!  A good One to you!
1669790 tn?1333662595
LOL , Hey Anne,  Happy New Year to you!
Avatar universal
And a VERY Happy New Year to you  both.  I hope it will bring you guys  complete recovery.   All my best thoughts
446474 tn?1446347682
Here is a video of a talk my hepatologist, Dr. Norah Terrault  gave on March 6, 2008 on the very issues you mention Will…

"Therapies for management of Hepatitis C in the pre-transplant patient"
Date: 3/6/2008
39 minutes

This program from UCSF is part of an annual update for physicians who care for liver failure/transplant patients. UCSF is a national leader among abdominal organ transplant programs. This segment covers therapies for management of Hepatitis C in the pre-transplant patient. (#14086)
At this part of Dr. Terrault’s presentation she is speaking of growth factors that are used to maintain cirrhotics on treatment who are more prone to treatment (peg-IFN & Riba) complications so that they were able to maintain on treatment without reducing Ribavirin or Peg-Interferon levels. Before anti-viral dose reductions had a big impact on SRV rates.

Dr. Terrault PowerPoint Side
At 13:30 into the presentation

Cytopenia Management

• Portal Hypertension – hypersplenism

• Use of growth factors advocated by experts but no controlled trials in cirrhotics
    * Use of epotein alpha in this population seems justifiable
    * GCSF used for neutropenia but unclear if risk of infectious complications reduced
• Thombocytopenia biggest factor
    * Splenectomy: case report only
    * Partial splenic embolization
    * Elthombopag (oral platelet growth factor)

“…Use of epotein alpha in this population seems justifiable as we know has a very direct relationship between having someone on epo and being able to maintain the ribavirin dose.
GCSF (Neupogen) is very frequently used for neutropenia but as I am sure you are all aware there is a very poor relationship actually between neutropenia and risk of infectious complications. Sometimes I really believe that when we treat with Filgrastim (marketed by Amgen as Neupogen) we are actually treating for ourselves more than for the patient. What I really believe is a more important issue in terms of treating infectious complications in cirrhotics is using prophylactic antibiotics. What we do in our practice for anyone that has cirrhosis and portal hypertension. That individual is on what is equivalent SBC prophylaxis….
Dr. Terrault Credentials:

Norah A. Terrault, M.D., M.P.H.
Liver specialist
Dr. Norah Terrault is a hepatologist and director of the Viral Hepatitis Center at the University of California San Francisco (UCSF) who is recognized internationally for the treatment of viral hepatitis and liver transplantation. Her research includes the study of viral hepatitis and its progression and treatment, especially in liver transplant patients. She is a clinical investigator participating in multiple studies of new antiviral therapies in patients with chronic hepatitis. Her studies in this area have been presented to the American Association for the Study of Liver Diseases, the leading organization for research in liver disease. She is currently of the board of AASLD.

163305 tn?1333668571
"GCSF (Neupogen) is very frequently used for neutropenia but as I am sure you are all aware there is a very poor relationship actually between neutropenia and risk of infectious complications. Sometimes I really believe that when we treat with Filgrastim (marketed by Amgen as Neupogen) we are actually treating for ourselves more than for the patient. What I really believe is a more important issue in terms of treating infectious complications in cirrhotics ..."

So how are those of us who are not cirrhotic, supposed to view this?
Is she saying, the doctors are covering their bases?

Inwardly I hate taking neupogen.
It would sure help if I understood it better.
446474 tn?1446347682

The point being that patients who are prone to cytopenias and infections (ie cirrhotics in doctor Terrrault's presentation) show no benefit by adding Neupogen to protect against infections.

Now that the antivirals are on the market we know that cytopenias are much more common in all patients (not just cirrhotics) treating with antivirals and peg-inf and riba.

So the point that both Dr, Terrault and Will's hepatologist is making is there is NO correlation between neutropenia and the incidents of infections in patients during treatment.

As I said before my own treatment experience as someone with compensated cirrhosis (so prone to cytopenias and infections) was to take Cipro to prevent bacterial infections while on treatment. An as a cirrhotic infections are always a concern since they can be life-threatening, the patient should have most current flu vaccine to prevent the most common viral infection as well.

Bottom line -
So if a doctor wants to prevent bacterial infections in a patient during treatment they should prescribe an antibiotic, not Neupogen.

Happy New Year!!!
I hope you are feeling better.
Avatar universal
So I have a question....is the Neuprogen a common drug they use for non-cirrhotics when their ANC drops below 500?  I just read a study where 87% of GT 1b's were administered this drug and reduced INF.  "Studies show that the drug Neuprogen was well tolerated"......what does "well tolerated" mean

Happy New Year to All!

Avatar universal
"Bottom line -
So if a doctor wants to prevent bacterial infections in a patient during treatment they should prescribe an antibiotic, not Neupogen. "

I wasn't clear from that video (which I think was made in 2007) if she meant that neupogen should never be used no matter how low the ANC. My impression was that she was saying that neupogen is overused, not that it should never be used. I didn't find the place on the video where she was totally black and white on her position about it's use. I didn't see where she included non-cirrhotics at all in her talk.

It seems to me that since that time experienced hepatogoligists who really know what they are doing as a result of research about the correlation between low ANC and infection have changed there threshold for using neupogen, but I don't think they never use it. Unfortunately many people are treated by doctors who don't fully know what they are doing or are as she suggested covering there a$$ by using neupogen too freely.

"So the point that both Dr, Terrault and Will's hepatologist is making is there is NO correlation between neutropenia and the incidents of infections in patients during treatment."
I believe she said the word "little" correlation, not "no" correlation in the video.

I am not cirrhotic, my WBCs and ANCs were normal prior to treatment, my ANC went to 280 at week 6 and I developed a bacterial infection in my ear and throat and was put on antibiotics and neupogen. I read about one person on this forum (can't remember who it was) whose ANC went to 0 and was hospitalized with bacterial pneumonia and put on intravenous antibiotics and neupogen. Although it seems obvious that neupogen is overused, I am not sure that it should never be used.

Prophylactic antibiotics in the high risk group seems to be more then subject of her comments which makes sense since the whole talk is about the importance of treating cirrhotics and and handling their complications.

Maybe you could ask her position on the rest of the treating population and neupogen, is there ever an appropriately low ANC threshold where she would advise using neupogen?  I can't imagine she is suggesting using prophylactic antibiotics in the whole treating population.  

148588 tn?1465778809
Cipro is good stuff. I used it effectively while on tx myself. It also appears to remain effective (especially if administered IV) even in the presence of neutropenia.


"Thirty patients had neutropenia, an abnormally low number of a type of white blood cell, the neutrophil. Ciprofloxacin was effective in 78 percent of patients.."

However, it appears to be most effective in the presence of a decent # of neutrophils.


"Neutrophils accumulate ciprofloxacin and other fluoroquinolones, a process that enhances the killing of intracellular pathogens and could facilitate the delivery of these agents to infection sites by migrating neutrophils."
Avatar universal
Thank H for passing along Terrault"s take on this. It would seem to me after what I have heard from these three different experienced Hepa"s  and what I have read from all the various studies and some that others have passed along here...the bottom line is  Filgrastim (neupogen) very well may be over prescribed in the HCV treatment regime.

I guess the bottom line is no doctor wants  their patient to pass away from runaway infection and no patient needs that added worry.even if it is an extremely rare event if ever(actually in the approx. 8000 that were studied this never happened that I saw )

In my own study there was no rescue for Neuts allowed and my ANC got to 540 and I asked "what now" ? they said if it get down to around <400 he would start me on an antibiotic( I don"t remember which one)

I asked him if that was not dangerous and he said "no" in 15 years of treating  he only had one patient that had a runaway infection and that person did not even have neutropenia and it would have happened to them probably regardless.

I guess the bottom line is anyone that has no underlying health issues or complications  that an experinced doctor would be worried about infection  then the automatic start of another powerful drug introduced should at the very least be questioned,,especially as Dave mentioned  "there seems to be a number of not so experinced doctors" taking on this treatment therapy.

desrt..I wonder what a decent # of neuts is? I read what you passed along and couldn"t seem to figure that out .thx.
Avatar universal
I guess the bottom line is no doctor wants  their patient to pass away from runaway infection and no patient needs that added worry.even if it is an extremely rare event if ever(actually in the approx. 8000 that were studied this never happened that I saw )


Meant to say : (actually in the approx.8000 that were studied it never happened that there was a runaway infection..).

not that  any had passed away   Passing away in a study is never that great for end result   :0)
419309 tn?1326503291
As an incidental note, will, my husband's ANC never hit the 500 mark and was never administered neupogen, but he did develop a rather problematic infection with ANCs in the 600s... he a minor scratch on his cornea, and with natural defenses low, the scratch ulcerated in 48 hours, and my husband would have lost sight in his right eye if not for aggressive antibiotics.  

I do believe it's a 'preventative' caution on the part of physicians... I think my husband was able to fight off the infection with antibiotics because he still had a reasonable amount of neuts, but it might have been a different outcome if he had more significant neutropenia. ~eureka
Avatar universal
I  would agree that this is a "preventative " measure  on the part of the physicians and  very well may be a good one and I am certainly glad your hubby staved off something that could have turned out nasty.
I guess that ties in a bit with the study  desrt posted that said the antibiotics need some vehicle to get around in. I wonder what the level could get down to .in order for there still to be effectivness.
Also I keep looking at these studies done and it seems there really has been very very miniscule problem with infection with low ANC...and then balanced against there being no free ride with any powerful drug as we all are aware......again like any med prescribed . Risk vs. benefit. always has to be looked at.

The doctor that prescribes Neup because you may be the 1 in 800 that "may get a runaway infection  probaly gives very little thought or most likey none at all  to what the drug he prescribes may do to  us 5 or 10 years from now....He most likely isn"t seeing you then... :0)
However I would agree neither you nor he wants there to be a disaster on "his " watch.  

Hope Hubby is doing ok  and  I wish all the best for you both in  2012


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