Reversibility of Hepatic Fibrosis and Cirrhosis--Is it all Hype?

[mikesimon]

"Now that the idea that hepatic fibrosis is reversible is taking root, many clinicians are beginning to ask why, if fibrosis is reversible, is there so little progress in the clinical setting, and will patients ever really benefit from antifibrotic therapies? Underlying such questions is a subtle cynicism that the reversibility of fibrosis and cirrhosis has been overhyped

[Tallahassee]

I think the Infergen trial is a good option. Go for it, if you can.

I'm also a non-responder to Interferon, but on Infergen I'm always UND, even though I did not have yet a sustained viral response.  I never reversed my fibrosis either, but I hope that may be Infergen slowed the fibrosis progression. If you care for the details, you may see my treatment history on the "roll call" tread by illo posted on 5/17or 5/18?

What I was thinking later...  For people like us (non-responders to regular interferon) Vertex treatment may be not a very promising option, since it seems relies on Interferon's power to fight mutated viruses.
It may be the best option for us to have Vertex (+ other polymerase/ protease inhibitors) with Infergen (or a combination of interferons). Also, it will be helpful, if they manufacture a pegalated infergen version.

I'm sorry for the Diabetes... It is hard to get rid of this bug (or rather RNA :)) without acquiring different side effects... unfortunately.

But anyway, I'm refusing to be negative!! :)
Have a wonderful day & holidays! (and for all members of the "club"!)

[BThompson4]

My transplanted liver went from F2 fibrosis one year prior to beginning SOC to "no significant fibrosis" (zero to F1) in a biopsy done during week 36 of treatment.  My hepatologist said to today that can happen but that biopsies can be unreliable in that they are small samples of your liver and that there could be areas of greater damage in the liver that were not sampled.  Biopsies can be unreliable.

[Dominic777]

Presented at the 2007 Digestive Disease Week (DDW) Meeting, May 19-24, 2007; Washington, DC.
This study was supported by Roche Laboratories.

Paul J. Pockros, MD1; Paul Martin, MD2; Ellen Lentz, PhD3; Fayez M. Hamzeh, MD, PhD3; and Anna Lok, MD, FRCP4
1Scripps Clinic, La Jolla, CA, USA; 2Mount Sinai School of Medicine, New York, NY, USA; 3Roche Laboratories, Nutley, NJ, USA; M1854 4University of Michigan Health System, Ann Arbor, MI, USA

"....Improvement in activity and/or fibrosis score was observed in 93 (86%) of 108 patients who achieved SVR, and in 45 (44%) of 103 patients who did not (P<.001).... Of those not achieving an SVR, 50% receiving 48 weeks vs 29% receiving 24 weeks therapy achieved 1 or more grade improvements in fibrosis or inflammation (staging and grading) (p=.049)...."

Introduction
Current treatment practice in HCV, aimed at achieving sustained virologic response (SVR), is to discontinue treatment in patients with detectable serum HCV RNA at 24 weeks.

Improvement in inflammation has been reported in patients with HCV who achieved SVR after receiving interferon with or without ribavirin, and in a smaller percentage of patients who failed to achieve SVR, suggesting that interferon has a direct effect on liver histology.1-4

Longer treatment duration may enhance histologic improvement regardless of SVR.

Study Objective
To determine if treatment of HCV genotype 1-infected patients with peginterferon alfa-2a plus ribavirin for 48 weeks is associated with a greater degree of histologic improvement than treatment for 24 weeks.

Author Conclusions
Among patients chronically infected with HCV genotype 1, those who achieved SVR after treatment with peginterferon alfa-2a plus ribavirin were more likely to have histologic improvement than those who did not.

The complete article:
http://www.natap.org/

[jmjm530]

For those not registered with MedScape, or otherwise did not read the complete article, the first paragraph quoted can be quite misleading as the article in its entirety is acutually quite positive.

First, the author acknowledges fibrotic reversal in SVRs which is the reason many of us treat. He writes: "...First of all, progress has been tremendous. The mere idea that fibrosis can regress when the initial disease is controlled or cured is exciting, given the decades of dogma that suggested scar formation was a unidirectional pathway. Ample evidence that fibrosis regresses with control of hepatitis B, hepatitis C, or other chronic liver diseases[2] attests to the tremendous regenerative power of the liver, and the rapid progress made in the development of targeted antiviral and disease-specific treatments..."

And the conclusion is equally postive, as the author says: "...So, hindsight indeed provides ample evidence of gratifying progress in hepatic fibrosis. Continued evolutionary development that changes our thinking about fibrotic liver disease and its prognosis is likely in the future. Revolutionary advances would certainly be welcome, but slow and steady gains should still justify hope without provoking hype..."

What the author appears to be saying is that while there may be some hype in this area, bottom line is that SVR has been shown to reverse Fibrosis and there have been "slow and steady" gains in other areas as well.

So to answer the author's own question as presented -- Is the reversiblity of hepatitic fibrosis and cirrhosis all hype? The answer is clearly no.

-- Jim

[mikesimon]

The article addresses the fact that not all cirrhosis is necessarily the same.

"This observation raises another challenging paradigm shift brought about by the growing evidence of fibrosis regression, namely that not all cirrhosis is the same; in fact, patients with cirrhosis can experience a widely variable clinical course. Our current staging methods do not, however, discriminate sufficiently between different degrees of cirrhosis. This oversight is understandable because until the past decade it hardly mattered whether a patient had 'early' or 'late' cirrhosis

[GoofyDad]

My hepatology transplant center certainly recognizes regression in cirrhotics as a potential outcome. They look at a 5 year timeframe for progress - not overnight. I asked why it took so long to recognize this and the responded it's because SVR is relatively new, SVR in cirrhotics, newer, and in other populations like alcoholics - the assault on the liver often was ongoing. In my case they gave me 50% odds of 2 stage regression over the long term.