Stage 1 to stage 3

[wantalivlong]

What is the shortest amount of time you've heard of someone going from stage 1 to stage 3 or 4?

Trying to guess how one is to know how long they should wait to treat OR if one should wait at all.

[Trinity4]

Jim,
Doc in Atlanta also said because I have stage 3 fibrosis, not cirrhosis, my chances of SVR were reduced.  Additonally, I did not clear at 12 wks so because of the advanced liver damage and not clearing, I was considered an excellent candidate for treatment extention.  I can't quote him verbatim, but it was discussed in length and his view is the more fibrosis you have as in stage 3, not cirrhosis,  SVR percentage is reduced.  

This a response from Dr. D as well:
Hi Dr D,

Thank you very much for taking the time to help people on this forum, like myself.

I am geno 1a, "at least" stage 3 (difficult to say for sure because one core was completely fibrous), white male, age 45, received hep c through a transfusion in 1981.  I am on tx currently, 180 Pegasys and 1400 ribavirin - I will take shot #30 tomorrow.  Besides liver enzymes, I had no hep c symptoms pre-tx.

Pre-tx VL - 718,581
week 4 - 193,000
week 8 - 30,000
week 13 - 1180
week 20 - 194
week 22 - 99
week 24 - <10 but detected
week 26 - <10 but detected
week 28 - Negative (=60 weeks after und - 100% (2/2)

The results from this study lead me to believe I should extend my treatment to 88 weeks.

So, am I a late responder or a super late responder?  Should I stop treatment or extend treatment?  If I extend treatment, how long should I extend?  Your opinion would be deeply appreciated, thanks!

smaug

by Douglas Dieterich, MD


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Douglas Dieterich, MD  
Male
New York - NY
Member since May 2008  



, Aug 04, 2008 07:42AM
To: all
As long as you get to < 10 and stay there I would generally treat for 48-52 weeks ( a year is what I tell my patients) after they become undetectable. I dont think you have to go to 88 weeks 72 should be plenty, but I would go at least that long because of the slow response and the fibrosis on the liver biopsy.  Good luck, that should work and then the fibrosis should reverse some too! DTD

[meki]

Megan - I rapidly progressed from NO HCV (was an EMT and had multiple blood work done) to less than 10 years later being extremely sick...........

I went from 0 to over stage 3 in that amount of time.

Keep in mind I'm a RARE drinker... Not even a six pack of beer a week --- all my life... Make that more like less than a 6 pack every 3 months even.

Anyhow - Each TX is different from what I understand from the multiple treaters.

Some folks have no side effects their 2nd or third TX - some have TONS.

It's individual...

As to whether you can reverse or not - I'm waiting to find out.

Meki

[susan400]

No problem, I just wanted to clarify the 'and cleared' part.  Take care, Susan400

[JennyPenny]

I know how hard you have tried to beat this virus. I am in the same place as you, although I already have cirrhosis and did when diagnosed in 1992. I've treated so many times I have lost count as well as beating up my bone marrow so I can never use interferon again.

I probably should have made myself clearer in my comment about cirrhotics never getting an improvement. I was definitely talking about in people who treated and cleared (and were Stage 4)......20% of them had a reversal of cirrhosis.

[bandman54]

meant stage.. .

bandman

[susan400]

The key words that you've said, "who cleared"....,   I have never cleared and my biopsies show no improvement either.  I've had 4 biopsies since 1994.  Last one was in spring of 2007.  Not everybody who treats, is fortunate enough to have a reversal in fibrosis, I am proof of that fact.  I do not drink, I do not smoke, I don't use illicit drugs, I eat a low fat diet and I exercise..., I've treated 10 times, and yet, I still have had no reversal on my fibrosis score.  I can look on the positive side in that I have been able to slow my progression to cirrhosis - but I chalk that up more to prayers by others and myself than I do to my treatments.    Susan400

[JennyPenny]

" WHILE you are still stage 3 the fibrosis can possibly be reversed. Once it becomes cirhhosis it cannot."

Actually the HALT C trials have shown that at year 5, SVR, 20% of people who cleared and were stage 4 have reduced fibrosis scores. Some have even gone back to no fibrosis. At Stage 3, 80% of patients have reduced their metavir score of 3 to a tage 2 or less.

[apache1]

To answer your above question Jim, no... the above study I posted was just on g2 , g3.

Interesting the study showed not only cirrhosis, but also stage 3 fibrosis, had a detrimental effect achieving SVR

apache

[jmjm530]

Understood. I was referring to your statement that "a grade 4 should treat now".

As mentioned, grade can fluctuate, so treatment decisions are usually based mostly on stage.

[bandman54]

stage 1 , grade 1

bandman

[susan400]

I do know have any idea which scale my biopsies were done under.  I've had 4 of them altogether.  I've had bridging fibrosis for the past 7 years.  I am now a genotype 1A, but previously was classified as genotype mixed of 1A/1B.   I am a 10 X   non-SVR treater.  I did have some response to the treatments in that my viral load would come down and my LFT's would come down, but I've never cleared.  Also, I've had no reversal of fibrosis on my biopsies.  There's really not much out there for me right now as far as available treatments.  Unless I get fortunate enough to be accepted into another Phase 2 or 3 trial.  I have no idea if by the time that these newer drugs are finally FDA approved if I'll even be able to get them.  Right now, I have no prescription drug insurance and if I even did, these new drugs are going to be costing such a high price that it's doubtful that many insurance companies will even want to pay for it.  My chances at having success at any further Telaprevir treatments is not all that great since I've already been exposed to the Telaprevir..., possible resistance factors there.  I don't mean to be negative, but facts are facts.  I can just try and stay as healthy as I can and hope and pray that I don't have further progression.

Susan400

[jmjm530]

I'm pretty well wrapped up on the "Treat now or Watch n' Wait" discussion, masked as something or another this time :) Hopefully people trying to make a decision will read this thread (and the referenced studies) carefully and then do their own independent research including discussing everything with a good hepatologist. And as I mentioned before, fibrosis progression and SVR -- whatever study or doc you believe -- is just one of many factors in coming to a decision.

As to Pearlman's "research", don't do it is all I can say! Absolutely no reason for an elective EOT biopsy. Haven't you put yourself through enough?

If you're really that curious -- and remember what it did to the cat -- why don't you wait a year or so post treatment when the liver may have had time to heal a bit more. And hopefully by then, Fibroscan or other non-evasive tests will be more readily available. Frankly, not even sure if I'd get scanned again if I walked into my doc's office and found a new machine sitting there. What's the point? I've already assumed my liver has healed some, so the result could only disappoint. I'm certainly not going to take any more interferon to heal it some more. LOL.

All the best,

-- Jim

[Trinity4]

Pearlman asked me if I would be willing to have another one at EOT.  Compiling research I guess.  I may just to that.  I certainly would have concrete evidence, one way or the other.

Trin

[nygirl7]

Good luck, that should work and then the fibrosis should reverse some too

Hopefully, treating 72 weeks will give the liver plenty of time to have the fibrosis reverse.  I wish I had gotten a biopsy as soon as treatment was over so I could have seen for certain what the situation was. I always intended to but........

[jmjm530]

Better one bird in your hand than ten birds in the forest.
------------------------------
There's another proverb that says a bird in your hand can sometimes lay an egg.

---------------
Apache,

Did they lump advanced 3's and 4's together. It looks like that at first glance. If so, then the two studies may be consistent because WIN-R does suggest that stage 4's have a tougher time with SVR.

-------------

Bandman,

Did you mean "grade 4" or stage 4? I don't think treatiment decisions revolve around grade. I had grade 4 around five years ago and grade 1 or 2 just before I treated. So it appears that grade can fluctuate a lot while stage tends to keep getting worse.

[bandman54]

I think it is worth trying the new treatments... if they would ever come out...

I do think a grade four should treat now.

I am a grade 1, stage 1 , so I am going to chill and hope they come out with the new meds soon.

bandman

[apache1]

This was from the AASLD 2008 Annual Meeting. This study shows a diffident difference in the time it takes for advanced fibrosis g2 and g3 to get a SVR

With advanced fibrosis the odds go down for g3 g2 in the below study, with shorter tx times, and SOC tx

Not sure if you could translate this to geno 1.
Just another study that shows something different than the other studies. Just something to think about.
This study spells out what they consider advanced fibrosis, Bridging fibrosis/cirrhosis was defined as metavir 3+4, Knodell 3+4, Ishak 4+5+6 on the pre-treatment liver biopsy.

http://publish.aasld.org/Pages/Default.aspx
AASLD 2008 Annual Meeting
#1239
Nov 03 8:00 AM - 5:30 PM
Q07. HCV: Treatment


Are there differences in treatment outcomes between HCV genotype 2 and 3 patients with advanced fibrosis treated with peginterferon alfa-2a (40KD) (PEGASYS®) plus ribavirin (COPEGUS®)?
S. Bruno1; S. J. Hadziyannis2; M. L. Shiffman3; D. Messinger4; P. Marcellin5
1. AO Fatebenefratelli e Oftalmico, Milano, Italy.
2. Department of Medicine and Hepatology, Henry Dunant Hospital, Athens, Greece.
3. Virginia Commonwealth University Medical Center, Richmond, VA, USA.
4. Biometrics, IST GmbH, Mannheim, Germany.
5. Hôpital Beaujon, Clichy, France.


Background: It has been previously shown that among patients infected with genotype 2 or 3 HCV treated with pegIFN alfa-2a 180µg/wk plus ribavirin (RBV) 800mg/day, rates of sustained virological response (SVR) are generally higher for G2 and overall 24wks of therapy is better than 16wks. The objective of this retrospective analysis of data from two large international phase III studies, is to extend these analyses to patients with advanced hepatic fibrosis infected with G2/3 treated with pegIFN alfa-2a plus RBV for 16 or 24wks.

Methods: G2/3 patients with advanced fibrosis/cirrhosis included in this analysis were those assigned to 16 or 24wks of treatment with pegIFN alfa-2a 180μg/wk plus RBV 800mg/day. Bridging fibrosis/cirrhosis was defined as metavir 3+4, Knodell 3+4, Ishak 4+5+6 on the pre-treatment liver biopsy. Responses were defined as rapid virological response (RVR;HCV RNA <50IU/mL at wk4), complete early virological response (EVR) (non-RVR but HCV RNA<50IU/mL at wk12), partial EVR (non-RVR with a detectable but ≥2 log drop in HCV RNA at wk12) and non-EVR (<2log drop at wk12). SVR was defined as HCV RNA <50IU/mL after 24wks of untreated follow-up.

Results: Data were available for 380 patients with advanced fibrosis/cirrhosis (G2 16wks=107; G2 24wks=99; G3 16wks=84; G3 24wks=90). Among patients treated for 16wks of therapy, SVR rates were 51% and 44% for G2 and G3 respectively and for 24wks of therapy SVR rates were 66% and 53% respectively. By MLR independent baseline factors predictive of SVR included lower body weight, higher alanine aminotransferase quotient, higher serum albumin level, higher platelet count, lower viral load, G2 infection and assignment to longer treatment duration. Among patients treated for 24wks, rates of RVR were substantially higher among G2 patients (Table). Rates of SVR among patients achieving an RVR and assigned to 24wks of treatment were 77% and 90% for G2 and G3 respectively and rates of SVR among patients achieving a complete EVR were 44% and 34% for G2 and G3 respectively. No patient with slower responses achieved an SVR.

Conclusions: Among patients with advanced fibrosis/cirrhosis treated with pegIFN alfa-2a plus ribavirin, those infected with G2 HCV had higher rates of RVR and SVR compared to patients infected with G3 HCV. For patients achieving an RVR and treated for 24wks, rates of SVR were high for both G2 and G3 (77–90%). For both G2 and G3 patients with advanced fibrosis/cirrhosis abbreviated 16-wk therapy was less effective and should be strongly discouraged in this patient population.

Response at wk 4/12                                  
                                           n=206 G3            n=174 G3

RVR, n(%)                                                      
                                           88 (50.6)             132  (64.1)

cEVR n(%)                           60 (34.5)                66 (32.0)    
            
pEVR, n(%)                          3 (1.5)                 9 (5.2)    

Non-RVR/EVR, n/N (%)        5 (2.4)                17 (9.8)
                  
            Abstract Central® (patent pending). © ScholarOne, Inc., 2008. All Rights Reserved.
Abstract Central and ScholarOne are registered trademarks of ScholarOne, Inc.

apache

[Megan5515]

So is it even worth it to try some of these new treatments?  I have stage 4 now.  When I found out I was already stage 2 and within a few years I was stage 3.  I have tried treatment 3 times with no success.  I was planning on discussing new treatments with my doctor in december.  I'm not sure if the side effects are worth it.

[zazza]

fibrosis progression that is.

[zazza]

Well, Jim, in Sweden we have a proverb that goes:

Better one bird in your hand than ten birds in the forest.

Meaning here that I'd rather treat now than wait for a tx that I do not know when it is coming and what it really means to me in terms of SVR and liver progression.

[bandman54]

I have a nurse friend that works with hep patiens and tx, ...
she says that she rarely sees rapid progression from 1 to 3.

It can happen, but it usually takes awhile.

Another thing to consider, and it may have already been mentioned, is..
tx can make the virus more difficult to get rid of the 2nd time around...

No one told me that.
Wish I had waited.

Now I am waiting on the polymerase inhibitors.

bandman

[jmjm530]

Thanks for posting, a few thoughts.

First, what a shame that prior non-responders or relapsers were subjected to a study that only treated them for 48 weeks, regardless of viral response. The 22% overall SVR rate is not surprising but one might argue irresponsible on the part of the study engineers.

Moving beyond that, this study as stated is for prior non-responders and relapsers and not for treatment naive's which I believe were what the much larger WIN-R study was comprised of. So again, we have apples to donuts and a much smaller sample size here.

But let's assume for agument's sake that the figures are correct. A seven point differential between let's day F2 and F3. Does this still make the argument that treating NOW is better than to Watch and Wait if you were say an F2? (And let's face it, that's what this is all about, it always is here :) )  Yes, seven points is significant IF one were to treat with the same drugs. But if in fact ones strategy was to wait and treat with better drugs (such as the PIs in trial) then that seven points should be wiped right out with HALF the exposure to interferon, given the promising PI trial results. So, as I see it, the case for selective Watch n' Wait is still quite intact even assuming this study is valid which the much larger WIN-R study suggests it might not be.

But again -- and a bit off track -- I have to wonder what these trial doctors disclosed to these poor patients to get them into this trial. Something wrong here, don't you think?

-- Jim

[zazza]

Take a look at this study. I just found it. It looks interesting.

"Platelet Count (and fibrosis stage) Predicts Sustained Viral Response (SVR) in the Re-Treatment of Previous Interferon/Ribavirin (I/R) Non-Responders (NR): Results from the EPIC3 Program"

http://www.natap.org/2008/EASL/EASL_61.htm

[jmjm530]

Thanks for the study, but only 188 patients were evaluated compared to with the WIN-R study, where 4913 patients were evaluated. It's also unclear from your study if they independently examined SVR at stage 4 (like with WIN-R) or if the more advanced stages were more or less lumped together as per earlier studies. It's unfortunate that the smaller study does not reference the opposing WIN-R results, as is often the case when a study seems to contradict a previous one, but it doesn't so one can only speculate on the "why's" but the two things I mentioned above -- sample size and fibrosis breakdown -- are what come to mind.

-- Jim