Pirfenidone effectively reverses experimental liver fibrosis

Background/Aims: Our group has been involved in searching for different strategies to ameliorate hepatic cirrhosis. The aim of this study was to evaluate the effect of Pirfenidone in the reversion or prevention of cirrhosis experimentally induced in rats by chronic administration of CCl4 and bile-duct ligation (BDL). Methods: Male cirrhotic Wistar rats (8 weeks of intoxication and then hepatotoxin was discontinued) received either oral saline or Pirfenidone at 500 mg/kg per day. Results: High levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase decreased significantly (P < 0.001) in animals treated with Pirfenidone (n = 11) with regard to saline-administrated animals (n = 9). Prothrombin activity and bilirubins were also reduced. Computerized fibrosis index demonstrated a 70% decrease (P < 0.001) along with less hydroxyproline content, reduction in activated HSC and higher active cell regeneration. A rearrangement of the parenchyma was also noted and gene expression of collagens I, III and IV, transforming growth factor β-1, Smad-7, TIMP-1 and PAI-1 decreased considerably in treated animals. Cirrhotic rats in which CCl4 was not discontinued displayed 40% liver fibrosis reduction. In a different cirrhosis model, 4-week BDL rats treated with the drug showed a significant 50% reduction in hepatic fibrosis (P < 0.01). Conclusions: This new drug might be useful in healing human disease. © 2002 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved