EFFECTS OF LONG-TERM ADMINISTRATION OF INTERFERON-ALPHA IN 2 MODELS OF LIVER FIBROSIS IN RATS

Background/Aims: The aim of this study was to assess the effect of the early and chronic administration of interferon alpha in the preventio n of hepatic fibrosis and portal hypertension. Methods: Rats with live r fibrosis due to bile duct ligation or CCl4 were divided into three g roups: sham, placebo and interferon alpha(2a) 100 000 UI/day. Liver fi brosis was assessed by the area of fibrosis (image analysis), liver hy droxyproline and mRNA (fibronectin, procollagen alpha 2(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 ex. There was a significant corr elation 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 sig nificant effects were observed in rats with biliary fibrosis, Conclusi ons: 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 antifibroti c effects of interferon need to be confirmed in further studies.