Development of an experimental model of liver cirrhosis in rabbits

1. The aim of the present study was to develop an experimental model of liv er cirrhosis in rabbits using CCl4 and phenobarbital. 2. Liver cirrhosis was induced in male New Zealand white rabbits (n = 10) b y intragastric administration of CCl4 once weekly starting 14 days after th e addition of phenobarbital to the drinking water (50 mg/day). Controls rec eived phenobarbital only (n = 7). Alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma -glutamyl transpeptidase (GGT), albumin and bilirubin levels were determined throughout CCl4 treatment. The initial dos e of CCl4 was 20 mug and subsequent doses were calculated to maintain AST a nd ALT levels between 400 and 800 IU/L for the duration of treatment (16 we eks). Indocyanine green (ICG) clearance was performed before and at the end of CCl4 treatment. Animals were killed at 16 weeks and three fragments of each liver lobe were processed for histological examination. A semiquantita tive score was used to evaluate the development of fibrosis. 3. Cirrhosis developed in 80% of rabbits treated with CCl4. These animals d id not gain weight compared with controls (P < 0.05). A significant reducti on of ICG clearance was observed in CCl4-treated rabbits compared with cont rols (P < 0.05). The AST, ALT, bilirubin and gamma -GGT levels were elevate d in CCl4-treated rabbits. 4. In conclusion, this model is successful in producing liver cirrhosis and may be useful in studies investigating metabolic, immunological or biochem ical changes during the evolution of chronic liver disease.