Effects of long-term administration of interferon α in two models of liver fibrosis in rats

Abstract

Background/Aims: The aim of this study was to assess the effect of the early and chronic administration of interferon α 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 α_2a 100 000 UI/day. Liver fibrosis was assessed by the area of fibrosis (image analysis), liver hydroxyproline and mRNA (fibronectin, procollagen α2(I)) contents, and serum hyaluronate. Systemic and splanchnic hemodynamics were also evaluated. Results: Interferon α 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 α. 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 α 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.