PERIOPERATIVE CONTINUOUS HEPATOCYTE GROWTH-FACTOR SUPPLY PREVENTS POSTOPERATIVE LIVER-FAILURE IN RATS WITH LIVER-CIRRHOSIS

Insufficient regeneration and dysfunction of cirrhotic liver following partial hepatectomy often make the resection extremely vulnerable to postoperative liver failure, which frequently leads to multiple organ failure. Hepatocyte growth factor (HGF), first identified as the most potent mitogen for primary hepatocytes, not only stimulates hepatic re generation but also accelerates liver function, improves fibrosis, and protects liver cells against injury. Therefore, we investigated the a bility of a continuous supply of HGF to cirrhotic livers to prevent po stoperative liver failure in rats. After liver cirrhosis was induced i n 40 rats by the intraperitoneal injection of dimethylnitrosamine (DMN ) for ii weeks, fibroblasts genetically modified to secret rat HGF or control fibroblasts were implanted in the spleens of 20 syngenic rats per group to supply HGF continuously and directly to the cirrhotic liv ers. Two weeks after the implantation, all rats underwent a 30% hepate ctomy. The HGF administration significantly improved liver fibrosis at the time of operation, attenuated the postoperative hepatic damage on histological examination, markedly accelerated the liver regeneration at 24 h after the hepatectomy. The blood chemical analysis indicated that HGF significantly suppressed postoperative liver failure. Most im portantly, the HGF treatment significantly improved the survival rate of the rats at 48 h after the hepatectomy, The perioperative continuou s supply of HGF from the spleen effectively prevented liver failure fo llowing resection of cirrhotic livers in rats. (C) 1998 Academic Press .