Hepatocyte growth factor supply accelerates compensatory hypertrophy caused by portal branch ligation in various types of liver

T Kaido, MD,a S Seto, MD, b H Oe, MD,c M Imamura, MDc

a Otsu Municipal Hospital, Otsu, Shiga, Japan b Takashima Municipal Hospital, Shiga, Japan c Department of Surgery and Surgical Basic Science, Kyoto University School of Medicine, Kyoto, Japan

AIM: Hepatocyte growth factor (HGF), first identified as the most potent mitogen for hepatocytes, significantly stimulates liver regeneration after hepatectomy. In this study, we examined whether HGF is also useful in accelerating compensatory hypertrophy caused by portal branch ligation in normal, jaundiced, and cirrhotic rats. METHODS: Normal, obstructive jaundiced, and dimethylnitrosamine-induced cirrhotic rats underwent portal ligation of the left lateral and median branches, supplying approximately 70 % of the total volume of the liver. Simultaneously, the animals were continuously treated with either recombinant human HGF (rhHGF) or vehicle alone via an intraperitoneally implanted osmotic pump. Two and 4 days after portal ligation, the degree of compensatory hypertrophy in unoccluded lobes was examined by measuring the wet weight ratios of the unoccluded lobes to the whole liver and the 5-bromo-2'-deoxyuridine labeling index of hepatocytes in each group. To examine the possibility of major hepatectomy in cirrhotic liver, the occluded lobes were resected 4 days after the portal ligation. RESULTS: The HGF treatment significantly increased the wet weight ratios and the DNA synthesis in nonoccluded lobes 2 and 4 days after portal ligation in each liver. rhHGF supply promptly decreased serum total bilirubin level in jaundiced rats. The HGF treatment markedly suppressed the posthepatectomy liver dysfunction and improved the survival rate of the cirrhotic rats at 48 h after the major hepatectomy. CONCLUSIONS: Continuous rhHGF administration accelerated compensatory hypertrophy in various types of liver and, especially, made extensive hepatectomy possible in cirrhotic rats.

KEY WORDS: portal ligation, compensatory hypertrophy, liver cirrhosis, major hepatectomy.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Metastasis.