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 regeneration but also accelerates liver function, improves fibrosis, and protects liver cells against injury. Therefore, we investigated the ability of a continuous supply of HGF to cirrhotic livers to prevent postoperative liver failure in rats. After liver cirrhosis was induced in 40 rats by the intraperitoneal injection of dimethylnitrosamine (DMN) for 4 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 livers. Two weeks after the implantation, all rats underwent a 30% hepatectomy. 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 importantly, the HGF treatment significantly improved the survival rate of the rats at 48 h after the hepatectomy. The perioperative continuous supply of HGF from the spleen effectively prevented liver failure following resection of cirrhotic livers in rats.
Kaido
T
T
Department of Surgery and Surgical Basic Science, Kyoto University School of Medicine, Japan. tokaido@kuhp.kyoto-u.ac.jp
Seto
S
S
Yamaoka
S
S
Yoshikawa
A
A
Imamura
M
M
D000818:Animals; D001774:Blood Chemical Analysis; D002455:Cell Division; D004128:Dimethylnitrosamine / Q000633:toxicity; D005347:Fibroblasts / Q000502:physiology / Q000637:transplantation; D015870:Gene Expression; D006498:Hepatectomy / Q000401:mortality; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000502:physiology*; D008099:Liver / Q000187:drug effects / Q000473:pathology / Q000601:surgery; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000150:complications* / Q000473:pathology; D017093:Liver Failure / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008115:Liver Regeneration / Q000502:physiology; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D013154:Spleen / Q000378:metabolism / Q000601:surgery; D015996:Survival Rate; D014162:Transfection
D017228:Hepatocyte Growth Factor; D004128:Dimethylnitrosamine