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  • Title: Effects of long-term administration of interferon alpha in two models of liver fibrosis in rats.
    Author: Fort J, Pilette C, Veal N, Oberti F, Gallois Y, Douay O, Rosenbaum J, Calès P.
    Journal: J Hepatol; 1998 Aug; 29(2):263-70. PubMed ID: 9722208.
    Abstract:
    BACKGROUND/AIMS: The aim of this study was to assess the effect of the early and chronic administration of interferon alpha in the prevention of hepatic fibrosis and portal hypertension. METHODS: Rats with liver fibrosis due to bile duct ligation or CCl4 were divided into three groups: sham, placebo and interferon alpha2a 100,000 UI/day. Liver fibrosis was assessed by the area of fibrosis (image analysis), liver hydroxyproline and mRNA (fibronectin, procollagen alpha2(I)) contents, and serum hyaluronate. Systemic and splanchnic hemodynamics were also evaluated. RESULTS: Interferon alpha significantly decreased fibrosis in the CCl4 model only: area of fibrosis: 13.9+/-3.7 vs 10.5+/-3.3% (p<0.05), hydroxyproline: 1.8+/-0.6 vs 1.2+/-0.2 mg/g wet liver (p<0.001), respectively placebo vs interferon alpha. There was a significant correlation between the area of fibrosis and hydroxyproline liver content (r=0.77 in the biliary model and r=0.87 in the CCl4 model, p<0.0001). Interferon decreased spleno-renal shunt blood flow (2.0+/-1.8 vs 0.9+/-0.7 ml/min; p<0.05) but not portal pressure in the CCl4 model. No significant effects were observed in rats with biliary fibrosis. CONCLUSIONS: The early and chronic administration of interferon alpha prevents the development of liver fibrosis and porto-collateral circulation in the CCl4 model but not in the biliary model. However, the antifibrotic effects of interferon need to be confirmed in further studies.
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