Alpha-interferon prevents liver collagen deposition and damage induced by prolonged bile duct obstruction in the rat

Abstract

Background/Aims: Interferons have been used to treat chronic viral hepatitis, due to their antiviral properties. However, interferons are now recognized also to inhibit collagen production. Since fibrosis has been associated with liver damage and dysfunction, the effects of interferon-α 2b on biliary obstruction-induced fibrosis were investigated. Methods: Extrahepatic cholestasis was induced in male Wistar rats (around 200 g) by double ligation and division of the common bile duct. Control rats were sham operated. Interferon-α 2b (IFN-α; 100,000 IU/rat) was administered subcutaneously, daily after surgery. The animals were killed after 4 weeks of bile duct ligation or sham operation. Liver damage and cholestasis was analyzed by histological, ultrastructural and biochemical techniques. Results: Biliary obstruction produced dilation of the bile canaliculi, disorganization of mitochondria and an increase in vacuolization. Bile duct ligation led to an important accumulation of collagen, determined, both histologically and as the hydroxyproline content of the liver. Bilirubin and serum enzyme activities (determined as markers of cholestasis) increased several-fold after bile duct ligation. Administration of IFN-α to bile duct ligated rats resulted in significant preservation of ultrastructure, histology, inhibition of collagen accumulation and in a partial improvement of serum markers of cholestasis. Conclusions: It is concluded that interferons possess interesting beneficial effects on the liver not related to its antiviral properties but probably associated with its antifibrogenic properties.