Less reversal of liver fibrosis after prolonged carbon tetrachloride injection.

BACKGROUND/AIMS: It was generally believed, but not proved, that early cirrhosis may be reversible, while advanced cirrhosis may not. This present study is to compare in mice the spontaneous regression of liver fibrosis between early and more advanced stage. METHODOLOGY: Liver fibrosis in mice was induced by intraperitoneal injection of carbon tetrachloride for 4, 10, and 16 weeks. After the last dose of each schedule, mice were sacrificed 1 day later (progression model) or left untreated for 10, 20, and 60 days (regression model). Tissue sections were stained by Sirius red. Liver hydroxyproline levels were determined to assess severity of fibrosis. Gelatinases in tissue extracts were assayed by zymography. RESULTS: During regression, diminution of fibrotic bands was more prominent in the 4-week group than in the others. Liver hydroxyproline levels in the progression model increased and resolution of liver fibrosis in the regression model decreased as carbon tetrachloride injection was prolonged. Liver matrix metalloproteinase-2 and -9 activities in the progression model also decreased as the injection was prolonged. CONCLUSIONS: These data demonstrated that reversibility of liver fibrosis would be gradually lost as liver injuries were prolonged. Gradual loss of the expression of matrix metalloproteinases may be responsible for the loss of reversibility.