Adenoviral vector expressing hepatocyte growth factor promotes liver regeneration by preoperative injection: The advantages of performing selective injection to the remnant lobe

Abstract

In a cirrhotic liver, the regenerative ability is impaired and liver failure may occur after a hepatectomy. Hepatocyte growth factor (HGF) stimulates liver regeneration and adenoviral vector expressing hepatocyte growth factor (AdHGF) allows hepatocyte growth factor (HGF) to be persistently expressed. The aim of this study is to evaluate the benefits of the selective and preoperative injection of AdHGF to the remnant lobes to regenerate the liver. A 70% partial hepatectomy was performed in dimethylnitrosamine-induced cirrhotic rats with a preoperative injection of AdHGF, adenoviral vector carrying beta-galactosidase (AdLacZ), or phosphate-buffered saline (PBS). The morphologic, histologic, and biochemical changes in the remnant liver and survival rates were then assessed. Portal injection with clamping the portal branches of the resected lobes for 5 min made it possible to effectively transduce the adenoviral vector into the remnant lobes. On day 7 after hepatectomy, the survival rates were 87% in the AdHGF group, 53% in the AdLacZ group, and 40% in the PBS group (P < .05). The ratio of the remnant liver weight/body weight (%) was 2.0 +/- 0.1 in the AdHGF group, 1.5 +/- 0.3 in the AdLacZ group, and 1.6 +/- 0.04 in the PBS group (P < .01). The 5-bromo-2'-deoxyuridine labeling index significantly increased in the AdHGF group on day 1, and the fibrous status significantly decreased in the AdHGF group on day 7 after hepatectomy. Preoperatively, the selective injection of AdHGF into the remnant lobes may be an effective treatment prior to a major hepatectomy in a cirrhotic liver.