Question about fibrosis improvement after SVR

[Andiamo1]

Any one know of any studies on this?  Anyone have any personal experience with it?

I am stage 3 - 4 transitional as of three years ago, so I am curious about what to expect if I have a SVR now.

Eric

[Andiamo1]

Jim: I agree with you.  I doubt I will do much of anything as long as I continue to feel better.

Eureka: thanks for posting the study.  I lived in Norwalk for 25 years and kept my boat in Westport, CT.  

[eureka254]

Article below relates to particularly transplant patients, but considering the scarcity of info relating to your question, I thought it might be of interest:

Title:    Sustained viral response to interferon and ribavirin in liver transplant recipients with recurrent hepatitis C  
Author:    Abdelmalek, MF  
Add.Author / Firpi, RJ  
     Editor:    Soldevila-Pico, C  
     Reed, AI  
     Hemming, AW  
     Liu, C  
     Crawford, JM  
     Davis, GL  
     Nelson, DR  
Citation:    LIVER TRANSPLANTATION 10 (2): 199-207 FEB 2004  
Year:    2004  
Abstract:    Recurrent hepatitis C infection is an important cause of progressive fibrosis, cirrhosis, and graft loss following orthotopic liver transplantation. Treatment for posttransplant recurrence of hepatitis C with interferon-based therapy is difficult but results in loss of detectable virus in up to 30% of patients. However, the durability of viral clearance and the associated histologic response in this setting is unknown. The aim of this study was to determine whether viral loss in response to antiviral therapy is durable and associated with improvement in liver histology. All liver transplant recipients who received interferon-based treatment for recurrent hepatitis C virus (HCV) at the University of Florida from 1991 to 2002 were included in this study. Patients who lost detectable HCV after treatment with interferon alone or in combination with ribavirin were followed to assess the durability of viral response and its impact on liver histology. One hundred nineteen transplant recipients were treated with interferon or combination therapy. Twenty-nine (20 men, 9 women; mean age, 54 yrs [range, 42-74 yrs]) lost detectable HCV RNA and remained virus negative for at least 6 months after discontinuing therapy (sustained viral response[SVR]). The mean follow-up after discontinuing therapy was 24.7 months (range, 6-70 mos).  
     Our study cohort included one patient with SVR following interferon monotherapy and 28 patients with SVR following combination therapy with interferon plus ribavirin. All patients remained HCV RNA negative (assessed by polymerase chain reaction or branched-DNA assay) during follow-up of up to 5 years. Liver histology assessed 2 years after treatment showed less inflammation compared with before treatment in 50% and showed no change in 38%. By 3 to 5 years post-treatment (n = 15 recipients), inflammation was reduced in 60% and remained unchanged in 33%. Fibrosis stage at 2 years improved by greater than or equal to1 stage in 27 %, remained unchanged in 38 %, and worsened in 35% despite viral clearance. At 3 to 5 years, the fibrosis stage had improved in 67%, remained unchanged in 13%, and worsened in 20%. Both grade of inflammation and fibrosis stage improved by 3 to 5 years posttreatment compared with baseline histology (p < 0.05). In conclusion, loss of HCV after treatment of recurrent chronic hepatitis C with interferon and ribavirin is durable, and the durability of the SVR is associated with improvement in hepatic inflammation and regression of fibrosis.

[eureka254]

An older article below from 2002 seems encouraging.  If I find more recent data, I'll be happy to pass it along.

"Impact of pegylated interferon alfa-2b and ribavirin on liver fibrosis in patients with chronic hepatitis C"
Author:    Poynard, T ;Add.Author: McHutchison, J  
Editor:    Manns, M., Trepo, C.,  Lindsay, K.,  Goodman, Z,,  Ling, M.H.,  Albrecht, J.
Citation:    GASTROENTEROLOGY 122 (5): 1303-1313, MAY 2002  
Year:    2002  
Abstract:    
Background & Aims: Liver fibrosis is an important prognostic factor in patients with hepatitis C. The effect of pegylated (PEG) interferon alone or its combination with ribavirin on fibrosis has not been established. Methods: We pooled individual data from 3010 naive patients with pretreatment and posttreatment biopsies from 4 randomized trials. Ten different regimens combining standard interferon, PEG interferon, and ribavirin were compared. The impact of each regimen was estimated by the percentage of patients with at least I grade improvement in the necrosis and inflammation (METAVIR score), the percentage of patients with at least I stage worsening in fibrosis METAVIR score, and by the fibrosis progression rate per year. Results: Necrosis and inflammation improvement ranged from 39% (interferon 24 weeks) to 73% (optimized PEG 1.5 and ribavirin; P < 0.001). Fibrosis worsening ranges from 23% (interferon 24 weeks) to 8% (optimized PEG 1.5 and ribavirin; P < 0.001). All regimens significantly reduced the fibrosis progression rates in comparison to rates before treatment. The reversal of cirrhosis was observed in 75 patients (49%) of 153 patients with baseline cirrhosis. Six factors were independently associated with the absence of significant fibrosis after treatment: baseline fibrosis stage, no or minimal baseline activity (OR 0.70; P = 0.02), and viral load < 3.5 millions copies per milliliter (OR = 0.79; P = 0.03).
Conclusions; PEG-interferon and ribavirin combination significantly reduces the rate of fibrosis progression in patients with hepatitis C.  

Hope that helps.

[jacksonblue]

treatment 1998 relapsed treatment 2004 72 weeks relapsed after neg for 47 weeks biopsy 1997 stage 1 biopsy done april 2007 for proof 3 no fibrosis detected could be sampling error doctor said must be some scarring arm a placebo proof 3 neg week 20 3.5 log drop week 12 finished treatment april 14 waiting to relapse for rollover my liver definetly inproved over 10 years relapsing twice

[jmjm530]

I had two Fibroscans. First was a few months into treatment and the second was four months post treatment. Results showed a drop from around a stage 3 to a very low stage 2. From what I've been told, a 1-2 stage drop is common with successful treatment. Personally, I would not have an evasive biopsy for curiosities sake and in fact am reluctant to have a non-evasive scan either. Unless I come up with a personal good enough reason to know, I'm just going to assume I've got a babies liver for now:)

-- Jim

[dranurag]

I did not get a second biopsy in last nearly two years. My stage was 3. I suspect if the next biopsy shows improvemnet it could just be a sample from an area with less fibrosis and other parts may be worse. Why  do we not take a muti core biopsy like in prostate?

[nygirl7]

WE've all always said at least a stage but I don't think that I can remember anyone who actually waited a year and went for the followup biopsy just to find out.  It would be good if they would ask us to do it - but at the cost and trouble...

I had intended to do it myself but never did.

Logically since the liver can improve it's condition and repair it would make perfect sense that it would. I hope. I pray. Can you imagine if in time we were all down to stage 0 LOL what a fantastic day that would be my friend!

[Willy50]

I have an aqaintance who was a stage 4 before TX, who cleared and then 2 years afterwards did a fibrosure (not a biopsy) and whose gastro pronounced them about a stage 2.  This was in a woman in her 40's.

I think until there are better means of testing both pre and post TX the results will be ancectdotal and subjective.  Frankly; I think they should do a study on the question.  Drug companies could use it as a means of "selling" the idea of treatment since it would be hard data.  People who are on the ropes trying to decide could perhaps be swayed into treatment.  The methodology may already be out there.  Since many people already have some sort of test (pre TX) the issue might only be in getting people who have completed TX into getting a post TX test of some sort.

Since most people aren't about to get another biopsy post SVR it would make sense to me that a fibroscan or fibrosure type non invasive test be done and regularly checked  following treatment.  I think it would be interesting to start creating some data on the subject.

It's a different topic but we also often suggest to people who fail TX that perhaps some damage was repaired during a treatment.  I have a few people that I know whose condition improved even in short and unsuccessful treatment.  And soooo..... the question might also be of use even for people who do not succeed with TX.

Once there is a database one could make some guesses about the effects of age, sex, and staging as they relate to regeneration.  

Yet another topic, but I would also be interested in seeing how post SVR drinking (or other drug usage) may affect regeneration.

Willy

[Andiamo1]

Thanks all for the information.

I did a google search before I posted this and only found outdated studies that were all over the place.  the problem is that the only way to determine the data for the study is a biopsy;  since it is invasive and not accurate in the sense that it only samples a small percentage of the liver, investigators have not much of a source of good data.  The general impression I got was that until some other source of data becomes available, there will be no definitive data on this subject.

Merrybe - I do not have portal hypertension.

[merryBe]

Hi Eric,my doc and all I've read suggests at least a one stage improvement, which you may be able to benefit with supplements as per HR's suggestions.

Part of it depends on how much liver was actually hardened stage 4, since that does not reverse itself. However, absent the irritanting virus, and other fibrotic stimulants such as alcohol, pot, and many prescription drugs we now know contribute to fibrosis, it would be reasonable to expect not so healthy liver cells to replace with higher quality cells, and not to continue  the scarring process between cell (fibrosis).

that's not to say that all veins would return to normal sizes, veins are not the most resilient things....so it would be worth a thourough check if you were wishing to return to flying or such.
But the liver will turn over and replace every cell in it (except scar tissue) every year and a half...so this is a reversible disease to a goodly extent in many cases.

Even if it could be only half reversed, you could live quite well on half a liver, given some care  in diet   etc. Women's livers are one third smaller on average, and we do pretty well
minus any disease with that size. So as long as you watch your weight/diet I say you wouldn't have an expiration date. The Liver is versatel and has already learned to route itself around non-functional tissue.
Have you got increased liver blood pressure yet??

[mremeet]

I don't know of any studies offhand, but I've always heard you can expect at least a stage regression and most accounts indicate more than that given good health habits and enough time (unless the liver is too far advanced into cirrhosis). From my quasi-fragmented memory I recall HR also indicating that he had anecdotally seen 2 stage regressions over a quite short period of time (like, a year or two?) with a few patients taking some variation of the antifibrotic regimen he recommended. I can't be certain of those details, but I recall something along those lines. I don't want to misquote him or mischaracterize what he said, so you might want to look into it before taking it as gospel. And he was cautious to qualify his observation as non-scientific and anecdotal, but still I think he had a sense of optimism based on his careful research that it could very well have occurred as a result of the suspected antifibrotic qualities of the substances these people were taking. I'd find out what the regimen was if you don't already know, and get on it. There's a reasonable possibility it will accelerate the healing process and help get your liver in tip top shape, sooner rather than later.

[Proactive]

There may be more recent data(thought I had seen a few articles supporting the improvement arguement), this is a bit dated, but it is from the 2002 FDA transcripts..While we all would like to believe there is a good deal of histologic improvement, I think the amount of improvement is still up to debate. But improvement does seem to get bandied about by the "top docs"
"DR. SJOGREN: And finally, I know we discussed a lot about liver biopsies and I wanted to point out because I may be incorrect and I know there are further studies that is looking at the possibility of improving the livelihood of our patients with Pegasys and with ribavirin, but in these studies although the biopsies with all the problems that we encountered doing biopsies, the first study had a 7 percent, calculate 7 percent improvement in fibrosis, so the majority of the effect we've been told on inflammation and the second study, I calculated by the numbers that were given by the FDA, a 15.6 percent improvement in fibrosis. And so when we look at long term in terms of cirrhosis and fibrosis, it's interferon now doing the job in terms of -- and I want to know if I'm correct in my percentages because you know I just used my hand calculator.

And so although I am a believer in that negative RNA and eliminating the virus is very much what I want to see in my patients, I'm using a different hat at this Advisory Committee and wanting to know if indeed these numbers, I mean they're very small in terms of improvement in the fibrosis and liver biopsies."
http://www.****.gov
PS: hope you are doing well....;^)Pro

[sldb]

As you know i  have well compensated stage 4 cirrhosis.  My hep has said i will have some rejuvination probably to stage 2.  My liver is greatly improved, back to normal size, enzymes wnl now for the last 2 yrs post tx.  Hep said there are some antifibrotics coming out in the near future and will let me know when availble.  Iam sure he will be involved in the studies,  I plan to rebiopsy 5 yrs post tx.  I will let you know when i hear something.  Leah