Tidbits from AASLD

[JennyPenny2009]

The following are things I picked up from various presentations and talks with the experts. You won't necessarily find them in abstracts or studies. Many docs just shared this info in their presentations. I just thought you'd like to hear the same things I heard. I also can't explain the reasons for some of this. So, for what its worth, here is what my notes say.

The RVR by 4 weeks and the week 12, 2 log drop rule, does not hold true for cirrhotics.  Cirrhotics need between 3 and 4 log drops by week 12 or they ALMOST definitely will not SVR. A 2 log drop at week 12 gives them less than a 5% chance to SVR.



Boceprevir will have about the same results for geno 1 patients as telaprevir but with anemia instead of rash. So it’s a toss up whether you want to see a hematologist or dermatologist during treatment.



People who drop their hemogloblin during the first 8 weeks and need epogen to continue, have a much better SVR rate than people who drop hemoglobin more slowly (not enough ribavirin?).



The natural history showing 10-20% going to cirrhosis is now 40%. For each decade over 40 years old, the chances of cirrhosis increase by approximately 10%,  Treat before the age of 40 and treat almost everyone.



People who SVR and get a histological benefit from Stage 3 or 4 to less than 3, still need to be screened every 6 months for HCC. Their risk does not fall to what it would have been if they never had stage 3 or 4 disease, but it is better than people who never SVR



Breakthrough is most common in genotype 1a’s.



Liver transplant patients have highest survival when they receive an African American liver.



Cirrhotics with platelets >125,000 have better chance of clearing virus than those with platelets <125,000.



People who have big drops in neuts from interferon should do prophylactic antibiotics with treatment.



Serious adverse events on interferon can lead to decompensation.



We have tests that show who will likely respond. They are not FDA approved yet. IL-28. CC's are the best results and have the genes that will make it more likely they will respond to interferon.

[mike716]

Jenny, do you feel that your repeated treatments, even though they didn't eliminate the virus, helped you to fight progression and survive?

Also: What did you mean when you said to Susan that you won't be young enough to do the protease and polymerase all oral treatments? I thought they were right around the corner. Will there be an age limit?

Mike

[JennyPenny2009]

I know you didn't dream it. I heard that in one of the presentations. Susan, please try not to worry too much. Think about me. HCV since 1966. Cirrhosis since first biopsy 1992. Many treatments, just like you. Never went below a 2 log drop. I'm still here. And you will be too. And you will be young enough to do the protease and polymerase all oral treatments. I won't.

[susan400]

I knew I didn't dream it.., here's the article I mentioned above:

http://www.medpagetoday.com/MeetingCoverage/AASLD/16735


Susan400

[susan400]

When I was clicking around the AASLD site with my mouse, trying to see if I could get any interesting info,... and I can't remember where it was that I saw this... I could have been under the research topic on the site??  Anyhow, it was something to the effect that women don't do as well with liver transplants with regard to graft rejection?  I really don't remember the exact wording, but it was something along those lines.  The statement you noted above about the progression after age 40..,  just a little bit scary for me.  Not that you can change that feeling..., I'm just saying it's my feeling.  Since I've just about been kicked to the curb with regards to being accepted into any other trials... and I'm 48 and have bridging fibrosis x 5 yrs..., all of these things jump around in my anxiety prone mind...   anyhow.  Thanks for the info you posted.  Susan400

[newleaf09]

It is the recent phase 3 boceprevir trial for naives.  Schering Plough provided all drugs, including the procrit.  It's at the local teaching hospital with one of their infectiious disease specialists as the investigating doctor for this particular site.  The trial was listed on www.clinicaltrials.gov.  Still there but not "active".There was a reference to using epoitin (procrit) in the informed consent.  They did not cover the other commonly used rescue drug for low neutrophils, filgrastim, but it was not forbidden and I got it through my insurance and nurse showed me how to inject it and did the bloodwork involved with it.  I think the key may be to be involved in a phase 3.  They (Schering Plough) learned about the potential for the anemia in their Phase 2, so provided the procrit for patients in the Phase 3.  The nurse just handed it out along with the other meds.  Sending you a message to your in-box.  Your platelet count would not have ruled you out of participation.

[mike716]

What did they do about your neutropenia?

[JennyPenny2009]

No, in fact I have never had any iron problems. And yes, my hematologist said he sees anisocytosis in many of his treatment patients. My problems were all with my white count.....I went down to zero neutrophils.

[mike716]

Tx caused your anisocytosis? You had no RBC or iron abnormalities (steatosis, high serum ferritin, etc.) before you started treatment?

[mike716]

Hi, newleaf! How exactly did that work? Did the people running the trial just tell the local hep MDs that they could give procrit to patients that were in the trial, and leave it at that?

Is the Boceprevir Phase III the only trial so far that has allowed procrit?

This is all rather important to me as I must make a decision very soon between SOC or a trial, and also which trial (PI vs polymerase inhibitors, Boceprevir vs Telaprevir vs all the other Pis, etc.). And my platelets are already down to 120,000, aside from the anisocytosis. Ifugure I'm sure to have serious anemia in a PI trial, so whether or not I can take procrit is probably going to make all the difference.

Mike

[JennyPenny2009]

I think a lot of people feel the same way you do about the doctors and with very good reason. I have been really lucky in that mine never puts anything off that might be of concern. My problem with the anisocytosis was no problem for me and both my hematologist and hep doc agreed. I had a bone marrow biopsy so I think they felt pretty assured that mine was treatment related and I was fine. the bone marrow biopsy was for something else, not the anisocytosis.

[newleaf09]

mike, the boceprevir Phase 3's included procrit, provided by the study itself.  I never dropped below 10.2 on SOC and boceprevir.  Still felt horrible but I was never endangered.  The use of procrit was at the doctor's discretion and I guess whenever I looked bad or seemed discouraged, they sent me home with procrit. Sorry to say I agree on your take on most MD's.

[banarep]

having been on telaprevir, the rash is one tough side.  at one point, i told the doc that it was a deal breaker and if something could not be done, i was off.  glad he found something.

[mike716]

I've learned the hard way not to give credence to doctors who say "not to worry". My hep MD said that when my transaminases were 10% above ULN, and then when they were 25% above, and even when they were 100% above. And he said the same for my platelets when they descended below the LLN. What doctors (whom I usually refer to as "saw-bones" and "pill-pushers") really mean is that they aren't going to worry. Whether it's worrying for the patient is another question.

Anisocytosis, or deformity of red blood cells, is associated with the body's misuse of iron and with anemia. These are conditions which, in a normal person, may not be too serious, but in us hep C infectees are of real concern, if not for a worsening of our liver disease then for treatment questions.

No abnormality in iron transport by RBCs is normal. It has some cause. And that cause may very well be of concern in hepatitis.

"Not to worry" is just MD c**p for "I don't know".

As far as I'm concerned, the anemia vs rash question in Boceprevir vs Telaprevir is a real matter of importance, especially as so many people become anemic on Tx and end up not clearing the virus because they have to drop the meds dose. And the trials won't let you use an escape drug for anemia.

Mike

[mikesimon]

Extended HCV Treatment After Liver Transplant Has Benefits

November 2, 2009 (Boston, Massachusetts) — After orthotopic liver transplantation for hepatitis C virus (HCV), extending antiviral therapy for 52 weeks after a first HCV-negative result leads to low relapse rates, according to research reported here during an oral presentation at The Liver Meeting 2009: American Association for the Study of Liver Diseases (AASLD) 60th Annual Meeting.

"In patients responding slowly to antiviral therapy following orthotopic liver transplant, the 'stop rules' at weeks 12 and 24 should be reconsidered," lead investigator Kimberly Brown, MD, head of the Division of Gastroenterology at the Henry Ford Hospital in Detroit, Michigan, and colleagues report in their meeting abstract.

[JennyPenny2009]

Thanks for that great explanation on the genetic variations. I dropped the ball on that one and did not get all the info. Appreciate your posting that.

[newleaf09]

Teleprevir vs. Boceprevir:  anemia responds to procrit and they found that including procrit in the course of treatment kept more people from dropping out.  I have a suspicion, though, that the people who suffered from the teleprevir rash (and not everyone did) had such an unmanageble rash that they quit TX over it.  That''s some bad rash to make you drop out of a life-saving course of treatment.  Glad to hear that the docs considered the 2 PI's equally effective.

A bit disconcerting to hear that once you've been at stage 2 or 4 that you will always need monitoring.  I guess it's like smoking; you're always considered more at risk for certain things even if you've been quit for 20 years.

pvk - there are 3 possible genetic variations for interferon response on a gene and it's very near the location that causes you to manufacture your own interferon.  You inherit either a C or a T from each parent, giving the offspring either CC (very responsive to IFN), CT (somewhat responsive) or TT (not responsive at all...the case for most African Americans).  The info comes from a study that was published in Nature online in August.  Here's a link to a popular article about the study:
http://www.nytimes.com/2009/08/17/health/research/17hepatitis.html

[justme53]

Interesting info AND rather sobering.

I was told last spring that if I didn't reach cEVR at 12 weeks that treatment would stop. They didn't care about log drops, it was UND or nothing. I had said that if I didn't clear, that I wanted to continue to 24 weeks, but it was not endorsed. Now I can see why.........

The 40 percent number for cirrhosis seems high, but more realitistic. I was also told that age and length of infection play a big role in progression, a fact that most likely played a role in my own case.. Add a few more pounds as we get older, metabolic syndrome..........double whammy.

Thanks for posting this...............

[JennyPenny2009]

I don't know the answer to your question. It's a good question for your doctor. A lot of people, including myself, have seen that word, anisocytosis, on lab sheets. My doc always said it doesn't mean a thing and to forget about it.

[mike716]

Hi, Jenny. You wrote: "Boceprevir will have about the same results for geno 1 patients as telaprevir but with anemia instead of rash." A person with red blood cell problems (I have anisocytosis, deformity of rbc), then, should probably do Telaprevir instead of Boceprevir. Is that right?

Cheers!
Mike

[JennyPenny2009]

I can tell you what I think, but my guess is just as good as yours. Mike, I am thinking that African Americans, while not responding well to treatment, also have a much slower rate of fibrosis and take longer to progress than Caucasians. Portann, it is the first I've heard of the rules not working. I know cirrhotics don't respond nearly as well but didn't know that their response at 4 and 12 weeks needs to be more robust. Also, my guess is that anyone who has serious adverse effects from treatment might be more in danger of decompensation but I think cirrhotics have the bigger worry since they are starting with a sicker liver and more cytopenias.

[pvk]

What are CCs?
-pvk

[mikesimon]

"Liver transplant patients have highest survival when they receive an African American liver. "

In an HCV patient?
That seems counter-intuitive considering the Afro American response to treatment.

Can you shed any light on this?

Mike

[annieCinMD]

Thanks for this, Jenny. Just got back from the study for my 12 week post checkup. Gives me stuff to keep in mind as a relapser and someone whose neuts tanked on interferon.

[portann]

I found each one of those comments so interesting and enjoyed having an insider's guide to the conference.

Lots to think about, especially about RVR/EVR/cirrhotics. Is that the first you've heard about that?

Do you think the statement "Serious adverse events on interferon can lead to decompensation", is a concern for someone who already has cirrrhosis or anyone with HCV doing tx?  

Thanks very much for sharing.

Susan