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43rd Annual Meeting of the European Association For The Study Of The Liver
Milan, Italy
April 23-27, 2008
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Regression of Cirrhosis Occurs & Prevents Death/Events
Reported by Jules Levin
EASL April 2008 Milan
V. Mallet1,2,3, H. Gilgenkrantz42,3, J. Serpaggi5, V. Verkarre1,4, A.
Vallet-Pichard1,3, H. Fontaine3, S. Pol1,2,3
1 Universite Paris Descartes, Paris, France;
2 INSERM U.567, Paris, France;
3 APHP, Hopital Cochin, Hepatologie, Paris, France;
4 APHP, Hopital Necker, Anatomopathologie, Paris, France;
5 Centre Hospitalier de Dreux, Dreux, France
The clinical impact of regression of cirrhosis is not known.
Has Regression of cirrhosis a clinical impact in chronic hepatitis C?

We have followed for a median 10-year period 89 consecutively treated patients with chronic hepatitis C who had Child A biopsy-proven cirrhosis.
96 patients with HCV-monoinfection and biopsy-proven cirrhosis were followed in this study. They received anti-viral therapy. A Sustained Viral Response (SVR) was achieved in 36.4% (n=35) and no SVR occurred in 61 patients (63.6%).
Patients who achieved a regression of cirrhosis with a followup 2nd biopsy (from METAVIR 4 to  
"Regression of cirrhosis prevents cirrhosis-related morbidity and mortality in hepatitis C-related cirrhosis while the risk of cirrhosis complications persists in long-term (SVR) responders with persisting cirrhosis. These results are the best evidence of the reversibility of cirrhosis and indicate that besides the sustained viral response, the fibrosis status of the patients is the main element to determine for the patientŐs prognosis."


The presenter said in 2006 we showed that regression of cirrhosis was accompanied by regression of portal hypertension and normalization of liver function tests.
They stratified based on the basis of the decrease of their histopathological fibrosis score in a post-therapeutic liver biopsy [performed 46 ± 26 months after the onset of treatment] and on their response to treatment.
Liver-related complications and survival rates were compared between patients with or without regression of cirrhosis (defined as a decrease from 4 to less than or equal to 2 METAVIR units) and between patients with or without sustained viral response (SVR).
19% (n=18) of patients had regression of cirrhosis and 81% (n=78) did not have regression of cirrhosis. The patients were followed up for a median of about 10 years.


Independent factors associated with regression of cirrhosis
Normal prothrombin time and SVR independently associated with cirrhosis regression:
* Prothrombin time 92.6% of normal in patients with cirrhosis regression vs 83.2% for those without cirrhosis regression
-- Odds ratio: 1.1 (95% confidence interval: 1.02-1.10)
* SVR 94% among those with cirrhosis regression vs 23% for those without cirrhosis regression
-- Odds ratio: 69.1 (95% confidence interval: 7.8-612.3)


The Main Study End-Point was:

--hepatic encephalopathy
--variceal bleeding
--spontaneous bacterial peritonitis
--hepatocellular carcinoma
--death from liver origin
SVR Results in Lower Number of Liver-Related Events (p=0.002)
HCV eradication provides enormous benefit in terms of survival and prevention of liver-related events, but there still are some events in the group with SVR. During the 10-year followup visual observation of the Kaplan-Meier curve shows about a 40% risk for liver-related events for non-responders (SVR), and about a 10% risk for responders. It looked like there were no events in the responder group until 72 months while events started occurring very quickly in the non-respionder group.
The incidence of liver-related complications, including HCC, was lower in patients with a sustained viral response (P=0.002 by the log-rank test) although three patients with persistent cirrhosis developed HCC.
No Liver-Related Events When there is Regression of Cirrhosis (p=0.01)
When patients are stratified on the basis of the second liver biopsy, with or without regression of cirrhosis, there are no liver related events; no complication occurred in the group of patients with regression of cirrhosis.
Overall Survival (death or transplantation): none with regression of cirrhosis
They stratified, that is looked at patients by SVR or no-SVR. Achieving an SVR showed an enormous benefit in terms of transplantation or survival but still 3 patients with an SVR developed HCC: one patient after 72 months, a 2nd patient after 120 months, and the 3rd after 192 months (15 yrs later).
When stratifying by histological response, non-reversers had a significantly worse outcome, and there were no events for reversers (death, transplantation), the followup in the Kaplan-Meier curve appeared to extend to 192 months (15 yrs).