Growth differentiation factor 15 as a marker of ineffective erythropoiesis in patients with chronic C virus infection

Abstract

Objective The aim of this study was to determine the expression of growth differentiation factor 15 (GDF-15) in patients with chronic hepatitis C virus and its association with iron-loading anemia in these patients. Background Significant shortened red cell survival has been reported in patients with liver diseases even in the absence of anemia. The mechanism for the observed decreased red cell lifespan is not fully understood, and it is most probably multifactorial. GDF-15, a member of the transforming growth factor-β super family, was first cloned from human monocytoid cell line and was found to inhibit tumor necrotizing factor production by macrophages and negatively regulate hepcidin. Recent studies suggest that GDF-15 levels increase in conditions of cell stress and apoptosis. In bone marrow (BM), GDF-15 increases in case of ineffective erythropoiesis. Patients and methods This study was carried out at Clinical Pathology Department, Faculty of Medicine and National Liver Institute, Menoufia University, in the period from May 2013 to May 2015. The study included 70 individuals: 50 patients with compensated chronic hepatitis C with unexplained anemia and 10 patients with idiopathic thrombocytopenic purpura who had normal red blood cell counts and no signs of erythroid dysplasia, as a control group for BM expression of GDF-15. In addition, 10 unrelated healthy age-matched and sex-matched adult individuals were included as a normal control group. Serum GDF-15 was measured by ELISA, and GDF-15 mRNA was measured by real-time RT-PCR. Results There were significant differences between the different studied groups regarding iron profile, GDF-15 serum level, and BM expression of GDF-15 mRNA, being higher in patients with chronic hepatitis C than other groups. GDF-15 was positively correlated with serum iron indices and negatively correlated with hemoglobin concentration. Conclusion Ineffective erythropoiesis contributes to iron overload and anemia in patients with chronic hepatitis C.