ALPHA-INTERFERON PREVENTS LIVER COLLAGEN DEPOSITION AND DAMAGE-INDUCED BY PROLONGED BILE-DUCT OBSTRUCTION IN THE RAT

Background/Aims: Interferons have been used to treat chronic viral hep atitis, due to their antiviral properties, However, interferons are no w recognized also to inhibit collagen production, Since fibrosis has b een associated with liver damage and dysfunction, the effects of inter feron-alpha(2b) on biliary obstruction-induced fibrosis were investiga ted. Methods: Extrahepatic cholestasis was induced in male Wistar rats (around 200 g) by double ligation and division of the common bile due t, Control rats were sham operated, Interferon-alpha(2b), (IFN-alpha; 100,000 IU/rat) was administered subcutaneously, daily after surgery, The animals were killed after 4 weeks of bile duct ligation or sham op eration, Liver damage and cholestasis was analyzed by histological, ul trastructural and biochemical techniques. Results: Biliary obstruction produced dilation of the bile canaliculi, disorganization of mitochon dria and an increase in vacuolization, Bile duct ligation led to an im portant 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-f old after bile duct ligation, Administration of IFN-alpha to bile duct ligated rats resulted in significant preservation of ultrastructure, histology, inhibition of collagen accumulation and in a partial improv ement of serum markers of cholestasis. Conclusions: It is concluded th at interferons possess interesting beneficial effects on the liver not related to its antiviral properties but probably associated with its antifibrogenic properties.