The Grade of Hepatic Fibrosis as a Predictor of Regeneration Activity after Partial Hepatectomy to Liver Cirrhosis in the Rat

Liver resection is the most effective method of therapy for hepatocellular carcinoma. We need accurate information about the liver function before liver resection, because most patients with hepatocellular carcinoma have associated liver cirrhosis in Japan. It has recently been reported that Transforming Growth Factor-β (TGF-β), which promotes liver fibrosis and suppresses the growth of hepatocytes, is related to the development of liver cirrhosis. So we focused our attention on liver fibrosis resulting from TGF-β, and investigated whether the extent of hepatic fibrosis (hepatic fibrosis index) might be correlated with hepatic regeneration activity after partial hepatecotmy in rats with thioacetamide-induced liver disease. Two groups of male Wistar rats (5 wk old) (10 to 30/group) were treated for 10 wk by weekly intraperitoneal administration of thioacetamide (200mg/kg, 3times/wk) or saline. All rats then underwent 70% hepatectomy under pentobarbital anesthesia. Hepatic regeneration activity was determined 24 and 48 hours after parital hepatectomy by means of bromodeoxyuridine incorporation into DNA. The hepatic fibrosis index was semiquantitatively calculated at the time of partial hepatectomy by automated images analysis on Azan-stained liver tissue. A significant inverse correlation was found between the hepatic fibrosis index and DNA synthesis in all rats (thioacetamide-treated and saline-treated) 24 and 48 hours after partial hepatectomy (r=-0.64 and-0.60, respectively; p