Erythropoietin stimulates hepatocyte regeneration after liver resection

Abstract

The increased relevance of liver surgery and transplantation as a therapeutic modality over the last two decades mandates the development of novel strategies to improve liver regeneration. Here we studied whether erythropoietin (EPO) improves liver regeneration after hepatectomy in pigs. Eighteen female pigs underwent laparoscopic left lateral liver resection and were allocated randomly into three groups. No EPO was administered to the control group (group 1, n=6). Group 2 (n=6) received EPO topically to the liver resection surface in a fibrin sealant. Group 3 (n=6) received EPO topically and systemically. Pigs were sacrificed 14 days after hepatectomy. The fraction of proliferating hepatocytes was determined by ki-67 immunostaining. Liver volume was determined by the principle of Archimedes, Liver weight and volume were significantly increased in group 3 (1249 ± 223 g, 1073 ± 190 ml) compared to group 2 (1027 ± 167 g, 894 ± 105 ml) and group 1 (923 ± 186 g, 813 ± 165 ml). Ki-67 immunostaining of liver tissue close to the resection surface demonstrated a significantly increased percentage of proliferating hepatocytes in group 3 (4.3 ± 1.96 %) and in group 2 (3.5% ± 0.98 %) as compared to group 1 (1.15 ± 1.2 %) 14 days after hepatectomy. Our results indicate for the first time that EPO supports liver regeneration after hepatectomy.