The only currently offered curative option for many patients with primary or secondary liver tumors is the resection of hepatic tumors. The aim of this study was to evaluate the role of recombinant human erythropoietin (rhEPO) in liver protection and regeneration after subtotal hepatectomy in rats. Rats undergoing 70% hepatectomy received an intraperitoneal injection of saline (control) or rhEPO (4 U/g) 30 minutes prior to resection. Liver function was assessed by the measurement of the international normalized ratio (INR) levels, and hepatic injury was assessed by serum alanine aminotransferase and aspartate aminotransferase levels. Hepatic apoptosis was assessed by intrahepatic caspase-3 activity and morphological criteria. The regeneration capacity of remnant livers was assessed over 7 days with the regenerated liver/body weight ratio, immunohistochemistry markers of cell proliferation (Ki-67) and angiogenesis (von Willebrand factor), and phosphorylated extracellular signal-regulated kinase signaling. Two and 4 days after subtotal hepatectomy, the regenerated liver/body weight ratio was significantly higher in animals treated with rhEPO versus the control group (P < 0.005). Serum liver enzymes and INR levels on days 2 and 4 post-hepatectomy were significantly lower in animals pretreated with rhEPO in comparison with the control group (P < 0.005). No statistically significant difference was noted in intrahepatic hepatic caspase-3 activity, immunohistochemistry for caspase-3, or a terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay between the hepatectomized groups. In the rhEPO-pretreated group, the mitotic index, Ki-67 and von Willebrand factor expression, and extracellular signal-regulated kinase activity were significantly higher on day 2 post-hepatectomy (P < 0.05) in comparison with the control group. In conclusion, rhEPO treatment may offer a unique beneficial dualfunction strategy for hepatic protection and regeneration immediately after subtotal hepatectomy in rats. Liver Transpl 16:631-638, 2010. V C 2010 AASLD.Received August 13, 2009; accepted January 24, 2010.Resection of hepatic tumors currently is the only curative option for many patients with primary or secondary liver tumors. Liver resection is limited, however, by the need to preserve a sufficient amount of functional liver because excessive resection leads to liver failure and death within a few days after surgery. 1-3 A prolonged prothrombin time, as determined by international normalized ratio (INR) levels, is therefore a common finding after major hepatic resection 3 The cirrhotic liver tolerates acute tissue loss poorly Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; BL, baseline; COX-1, cyclooxygenase 1; EPO, erythropoietin; ERK, extracellular signal-regulated kinase; HPF, high-power field; IjB, inhibitor of nuclear factor kappa B; INR, international normalized ratio; I/R, ischemia/reperfusion; JNK, Jun amino-terminal kinase; LBWR, liver/body weight ratio; NFjB,...

No abstract