Effects of erythropoietin and iron on late-phase liver regeneration after partial hepatectomy

Abstract

Liver regeneration after 70% partial hepatectomy (PHx) is a clinically significant repair process for restoring the proper liver architecture. Promising strategies to maximize liver regeneration are clinically applicable as curative options for patients undergoing resection of primary or secondary hepatic cancers. Although some studies demonstrated that recombinant human erythropoietin (rhEPO) and iron have been shown to improve liver regeneration at the early-stage after PHx, their combination effect has not been elucidated at the late phase of liver regeneration and function. Rats subjected to PHx after anesthesia were subcutaneously administrated with rhEPO (3,000 IU/kg) alone, rhEPO in combination with intravenous infusion of iron isomaltoside (40 mg/kg), or an equal volume of physiologic saline. The liver and blood were carefully obtained on days 7 and 14 after resection. Hepatocyte proliferation and liver regeneration were assessed by immunohistochemical staining for Ki-67 and liver/body weight ratio, respectively. In addition, complete blood counts and serological factors associated with liver function and toxicity were evaluated using an automated hematology analyzer and enzyme-linked immunosorbent assay kits. rhEPO effectively enhanced late-phase liver regeneration and liver function without any hepatotoxicity in 70% hepatectomized rats, and those effects were further enhanced by co-administration with iron isomaltoside. Thus, the combination may synergistically improve the late-phase liver regeneration and liver function in patients undergoing surgical treatment of hepatic diseases, including hepatic cancers and liver cirrhosis.