Long‐term administration of interferon‐α in non‐responder patients with chronic hepatitis C: follow‐up of liver fibrosis over 5 years

Abstract

In chronic hepatitis C, previous data have shown that short-term treatment with interferon-alpha (IFN-alpha) can reduce collagen deposition in the liver independently of the viral response. The aim of this work was to determine, in non-responder patients, the long-term effect of IFN-alpha on liver fibrosis according to the total administered dose and the fibrotic stage. Fibrosis was investigated on liver biopsies from 24 non-responder patients with chronic hepatitis C retreated with successive courses of IFN-alpha. The degree of liver fibrosis was assessed on three successive biopsies, performed before IFN-alpha treatment and 1 and 5 years later, in 13 and 11 patients, respectively, treated for less (mean: 7.5 months, 313 MU) and more (mean: 21.8 months, 791 MU) than 1 year. For each biopsy, fibrosis was assessed using a histological semiquantitative fibrosis scoring system and by morphometry after picrosirius red staining. Regardless of the dose and duration of IFN-alpha therapy, a slight decrease of fibrosis was observed in patients 5 years after starting treatment. In cirrhotic patients, a short treatment induced an improvement followed by a relapse of fibrosis in 57%, and only 43% of patients showed constant collagen regression over the 5 years of follow-up. On the contrary, after prolonged therapy, a progressive and significant decrease occurred throughout the follow-up period in all patients (P = 0.045). Long-term treatment with IFN-alpha is therefore associated with regression of liver fibrosis, particularly in cirrhotic patients. These promising results need to be confirmed in a larger series of patients.

Effect of interferon-alpha on experimental septal fibrosis of the liver - study with a new model

“…Results were then slightly suggestive of an antifibrogenic effect, being statistically significant on Differences between the control group and each one of the treated groups are highly significant (P< 0.05-Student-Newman-Keuls); INF-α: interferon-α Differences between control (Group IV) and groups II and III are highly significant (P< 0.05, morphometric grounds only. Such discrepancy of results with different methods of fibrosis evaluation has also been observed in human studies when the anti-fibrotic effect was rather mild (Guerret et al 1999). However, a clear-cut, dose-depend effect became evident when the animals were treated with 500,000 and 800,000 IU.…”

“…The decrease in the amount of fibrosis was recorded even in non-responders to the anti-viral treatment and was seen to occur regardless of viral load, and the presence of inflammatory or degenerative changes (Guerret et al 1999). Nevertheless, it remains rather difficult to determine from such clinical studies whether the effect on fibrosis was indeed direct or merely secondary to modulatory and anti-viral properties of the drug.…”

Early decrease in serum IV-7S levels during IFN treatment predicts anti-fibrogenic effect in nonresponders with chronic hepatitis C

“…9,11 On the other hand, the effect of IFN on the long-term outcome of patients, including the suppression of progression to cirrhosis or the prevention of HCC, has recently been reported. 9,11,[17][18][19][20][21][22][25][26][27] These reports suggest that IFN treatment has a suppressive effect on disease progress, irrespective of whether or not HCV is eradicated.…”

Histological response study of chronic viral hepatitis C patients treated with interferon alone or combined with ribavirin

“…Furthermore, it has also been proven through several clinical trials that interferon-based treatments provoke histological improvements, even in virological non-responders [17][18][19][20][21][22]. We evaluated hepatic fibrosis and necro-inflammatory activity progression in chronic hepatitis C patients who were nonresponders to interferon-based treatments or relapsers.…”