Treatment of cirrhotic rats with epidermal growth factor and insulin accelerates liver DNA synthesis after partial hepatectomy

Prevention of postoperative hepatic failure is important after hepatic rese ction. In patients with cirrhosis, impaired liver function and regenerative capacity after major hepatic resection are associated with increased morbi dity and mortality. In this study, a combination of epidermal growth factor (EGF) and insulin were used as hepatotrophic factors in an attempt to stim ulate DNA synthesis after 70% hepatectomy (HTX). Regenerative capacity was evaluated in normal and cirrhotic rat liver by measuring DNA synthesis in v ivo. Micronodular liver cirrhosis was established by the simultaneous oral administration of CCl4, and phenobarbital. Epidermal growth factor plus ins ulin was injected subcutaneously immediately after and 12 h after HTX or sh am operation was performed. Rats were killed 24 h after the operation and l iver regeneration was estimated by [H-3]-thymidine incorporation into DNA a s well as an autoradiographic nuclear labelling index. Hepatectomy increase d [H-3]-thymidine incorporation significantly in both normal and cirrhotic rats. In cirrhotic rats, [H-3]-thymidine incorporation after HTX was signif icantly lower than in normal rats and administration of a combination of EG F and insulin after HTX enhanced [H-3]-thymidine incorporation. In conclusi on, DNA synthesis 24 h after HTX is decreased in cirrhotic rats compared wi th normal rats and EGF supplementation with insulin accelerates DNA synthes is in hepatectomized cirrhotic rats. The data suggest that administration o f combinations of exogenous hepatotrophic factors may play a useful role in the treatment of cirrhotic patients undergoing major hepatic resection.