PORTAL BRANCH LIGATION WITH A CONTINUOUS HEPATOCYTE GROWTH-FACTOR SUPPLY MAKES EXTENSIVE HEPATECTOMY POSSIBLE IN CIRRHOTIC RATS

In a cirrhotic liver, the regenerative ability and specific functions are so impaired that excessive resection easily complicates postoperat ive liver dysfunction, which frequently leads to life-threatening mult iple-organ failure. Hepatocyte growth factor (HGF), first identified a s the most potent stimulator of DNA synthesis in primary hepatocytes, not only stimulates liver regeneration, but also accelerates hepatic f unction, improves fibrosis, and protects liver cells against injury. T herefore, we investigated the efficacy of preoperative portal branch l igation (PBL) (which can induce compensatory hypertrophy of the unaffe cted lobes) combined with a continuous HGF supply in the performance o f extensive hepatectomy in cirrhotic rats. Cirrhosis was induced by in traperitoneal injections of dimethylnitrosamine (DMN) three times per week for 3 weeks. Five days after the last injection, when 70% hepatec tomy is lethal, the rats underwent portal ligation of the left lateral and median branches (corresponding to approximately 70% of the total volume of the liver). Simultaneously, they were continuously treated w ith either recombinant human HGF (rhHGF) or vehicle from an intraperit oneally implanted osmotic pump. Four days after the portal ligation, t he occluded lobes were resected, The HGF treatment rapidly increased b oth the wet weight of the unoccluded lobes and the hepatocellular DNA synthesis. The blood chemical analysis indicated that HGF significantl y suppressed the posthepatectomy liver dysfunction. Most importantly, the HGF treatment markedly improved the survival rate of the rats at 4 8 hours after the major hepatectomy In conclusion, PBL combined with a continuous HGF supply makes extensive hepatectomy possible in cirrhot ic rats, mainly by promoting the hypertrophy of the unaffected lobes.