dirrhosis regression

[wrayc]

This example is instance of HBV.

question now, it it applicable to HCV?

Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study.
Marcellin P, Gane E, Buti M, Afdhal N, Sievert W, Jacobson IM, Washington MK, Germanidis G, Flaherty JF, Schall RA, Bornstein JD, Kitrinos KM, Subramanian GM, McHutchison JG, Heathcote EJ.
Source
Service d'Hépatologie, Hôpital Beaujon, INSERM Unit CRB3, Clichy, France. patrick.***@****
Abstract
BACKGROUND:
Whether long-term suppression of replication of hepatitis B virus (HBV) has any beneficial effect on regression of advanced liver fibrosis associated with chronic HBV infection remains unclear. We aimed to assess the effects on fibrosis and cirrhosis of at least 5 years' treatment with tenofovir disoproxil fumarate (DF) in chronic HBV infection.
METHODS:
After 48 weeks of randomised double-blind comparison (trials NCT00117676 and NCT00116805) of tenofovir DF with adefovir dipivoxil, participants (positive or negative for HBeAg) were eligible to enter a 7-year study of open-label tenofovir DF treatment, with a pre-specified repeat liver biopsy at week 240. We assessed histological improvement (≥2 point reduction in Knodell necroinflammatory score with no worsening of fibrosis) and regression of fibrosis (≥1 unit decrease by Ishak scoring system).
FINDINGS:
Of 641 patients who received randomised treatment, 585 (91%) entered the open-label phase, and 489 (76%) completed 240 weeks. 348 patients (54%) had biopsy results at both baseline and week 240. 304 (87%) of the 348 had histological improvement, and 176 (51%) had regression of fibrosis at week 240 (p<0·0001). Of the 96 (28%) patients with cirrhosis (Ishak score 5 or 6) at baseline, 71 (74%) no longer had cirrhosis (≥1 unit decrease in score), whereas three of 252 patients without cirrhosis at baseline progressed to cirrhosis at year 5 (p<0·0001). Virological breakthrough occurred infrequently and was not due to resistance to tenofovir DF. The safety profile was favourable: 91 (16%) patients had adverse events but only nine patients had serious events related to the study drug.
INTERPRETATION:
In patients with chronic HBV infection, up to 5 years of treatment with tenofovir DF was safe and effective. Long-term suppression of HBV can lead to regression of fibrosis and cirrhosis.
FUNDING:
Gilead Sciences.

[wrayc]

Thanks everyone for the replies

sorry for the confusion on the obvious spelling error. I made the post hastily and discovered there is no edit feature.

The point of the post wasn't so much regarding the disparities between the two viruses, such as modes of transmission or treatment, RNA vs. DNA virus etc, but rather to highlight the oft raised issue of cirrhosis, a common feature of both viruses and regression of cirrhosis after treatment. I noted this to be very common question/debate among patients and HCP's alike.

Some of us may have a clinical background or not but, in the end, I guess we never quite stop learning, not to mention the research is ongoing and information does change over time. Thanks again mikesimon for the spot on post and cited article and others' input as well.

On a side note, regarding the issue of interferon, I think its possible to cite the risks regarding its use without the possibility of "fear mongering".  The issues are quite real, such as the points made here of potentially increased  or more rapid progression of cirrhosis following unsuccessful treatment as well even an increased risk of death from 6% to 10% of those treated with interferon vs. placebo or untreated, again, among those unsucessfully treated. I think we all look forward to the possibility of treatment without interferon that will eventually become reality within the near future. Some may even be waiting for that time to treat. Whichever the case, it's always good to have all the facts to make well informed decisions

[mikesimon]

"Some recent research suggests that INF non-responders have increased long-term rate of liver damage following INF treatment, as compared to those that never treated."

I've only read the abstract which I posted below but from what I see I don't believe that the conclusion follows logically.

One possible inference is that non-responders simply have an increased long term rate of liver damage than the typical/average HCV positive patient. Did exposure to interferon accelerate the damage or is the accelerated damage associated with the non-responder host characteristics? Of course, it's probably impossible to determine if one is a non-responder if they aren't treated with interferon/ribavirin but the conclusion that the interferon was the cause of the damage doesn't seem to necessarily follow. I think it is safe to assume that the untreated cohort consisted of responders and relapsers as well as non-responders. I am suggesting that it is possible that if non-responders could be identified before treatment we might find that non-responders do worse regardless of whether they were treated with interferon. It might just be the nature of non-responders. I do not know this but it seems as though the possibility should be considered.



"The long-term consequences of failed interferon-alpha based hepatitis C treatment on liver morbidity and survival have not been fully explored. We performed retrospective analyses to assess long-term clinical outcomes among treated and untreated patients with hepatitis C virus in two independent cohorts from a United States Veterans Affairs Medical Center and a University Teaching Hospital. Eligible patients underwent liver biopsy during consideration for interferon-alpha based treatment between 1992 and 2007. They were assessed for the probability of developing cirrhosis during follow-up using Cox proportional hazards models, stratified by pretreatment liver fibrosis stage and adjusted for known risk factors for cirrhosis and characteristics affecting treatment selection. The major predictor was a time-dependent covariate for treatment outcome among four patient groups: 1) patients with sustained viral response to treatment; 2) treatment relapsers; 3) treatment nonresponders; and 4) never treated patients. Treatment nonresponders in the Veterans cohort had a statistically significantly increased hazard of cirrhosis (HR = 2.35, CI 1.18-4.69) compared to never treated patients during a mean follow-up period of 10 years. In a replication cohort from the University Hospital, nonresponders also had a significantly increased hazard of cirrhosis (HR = 5.90, CI 1.50-23.24) during a mean follow-up period of 7.7 years. Conclusion: These unexpected findings suggest that hepatic inflammation and fibrosis may be accelerated by interferon-alpha based antiviral therapies in patients who fail to clear the hepatitis C virus."

http://liverlearning.aasld.org/aasld/2012/thelivermeeting/24360/myrna.cozen.nonresponders.to.interferon-based.treatment.of.hcv.exhibit.an.html?history_id=124860

[can-do-man]

"Some recent research suggests that INF non-responders have increased long-term rate of liver damage following INF treatment, as compared to those that never treated."

One would think it is reasonable to assume that anyone that still has Hep C their liver will continue to get worse, I hope your not suggesting one does not risk treating. Maybe you are unaware of what comes next? Like ESLD. As studies that were just posted suggests those that do gain SVR (cured) not only does the damage stop but Regression of Cirrhosis is possible............

[rambleon40]

Some recent research suggests that INF non-responders have increased long-term rate of liver damage following INF treatment, as compared to those that never treated.

http://liverlearning.aasld.org/aasld/2012/thelivermeeting/24360/myrna.cozen.nonresponders.to.interferon-based.treatment.of.hcv.exhibit.an.html?history_id=124860

see also:

http://www.hepmag.com/articles/interferon_retreatment_2501_23442.shtml


At last year's American Association for the Study of Liver Disease (AASLD)  annual meeting, a number of researchers presented articles that made significant challenges to the cure rates claimed by manufacturers of INF / ribavirin / telepravir / boceprevir in random controlled trials (RCTs).

Finally, always check the funding and question the source.  Your study (Hep B, not C as pointed out) was funded by Gilead, the manufacturer of Tenofavir.  Always a factor to consider when determining what weight to give report.

http://en.wikipedia.org/wiki/Tenofovir

[mikesimon]

Regression of Cirrhosis in HCV

Study findings suggest that HCV treatment can lead to regression of cirrhosis.

Treatment of chronic liver disease is known to halt histologic damage. In addition, some evidence suggests that treatment of underlying hepatitis C virus (HCV) infection might lead to regression of fibrosis and cirrhosis. Now, investigators at a single tertiary care center in France have studied this possibility further.

The study cohort comprised 96 HCV-positive patients with biopsy-proven cirrhosis who received HCV treatment between 1988 and 2001 and were followed up every 6 months (median, 118 months). All patients were monoinfected, had Child-Pugh class A cirrhosis, and received conventional or pegylated interferon with or without ribavirin. Follow-up liver biopsies were performed a median of 17 months after the end of treatment. The main outcome measure was a composite endpoint of liver-related complications (ascites, encephalopathy, variceal hemorrhage, spontaneous bacterial peritonitis, hepatoma, liver transplantation) or death from liver-related causes. Regression of cirrhosis was defined as a decrease in fibrosis stage from 4 to 2 or lower on the METAVIR scoring system.

Forty-one percent of patients achieved sustained virologic responses. Cirrhosis regressed in 19% of patients. The incidence of cirrhosis-related complications per 100 patient-years was 0 in patients with regression of cirrhosis and 4 in patients without regression (P=0.002). Transplant-free survival at 10 years was 100% in patients with regression of cirrhosis and 74.2% in patients without regression (P=0.025).
Comment

Although this study was limited by its retrospective design and the small number of cases of cirrhosis regression (which precluded the analysis of other confounding factors), the findings suggest that HCV treatment can lead to such regression. More important, regression of cirrhosis is associated with a significant reduction in morbidity and mortality. Clinicians should include this information when counseling patients regarding the potential benefits of HCV treatment.

http://www.jwatch.org/jg200811210000002/2008/11/21/regression-cirrhosis-hcv

[can-do-man]

If your talking about regression of cirrhosis and HCV here's a good read that Rivll posted............. http://hepatitiscresearchandnewsupdates.blogspot.com/2013/06/sustained-virologic-response-for.html#.UbU0pthu4mw

Remember the key is to first become SVR.........

[notsoeasy]

Maybe he just posted an example, but the real question is about regression of cirrhosis?
I

[HectorSF]

No. Hepatitis B and hepatitis C are two very different viruses and have little in common. Treatments used are totally different and no one treats hepatitis C for 5 years. Hepatitis C is curable. Hepatitis B is not. So this makes most of the information above irrelevant to hepatitis C treatment and cirrhosis.

If you have a question about cirrhosis and hepatitis C than ask it.

Hector