Lower serum prohepcidin levels associated with lower iron and erythropoietin requirements in hemodialysis patients with chronic hepatitis C

BACKGROUND Patients with chronic HCV infection have increased liver iron. Recently identified protein hepcidin synthesized in the liver, is thought to be a key regulator for iron homeostasis and is induced by infection and inflammation. Lower erythropoietin and iron supplementation requirements were previously reported in HD patients with HCV infection. We investigated the association of prohepcidin with inflammation and iron parameters in HD patients with and without chronic HCV infection. METHODS Sixty patients (27 male, 33 female, mean age 50±15 years) on chronic HD were included. Parameters related to iron metabolism (ferritin, serum iron and total iron binding capacity (TIBC)), inflammation (hs-CRP, TNF-α and IL-6) and prohepcidin levels were measured. The response to treatment (erythropoiesis-stimulating agent (ESA) resistance index) was assessed from the ratio of the weekly erythropoietin (rhuEPO) dose to hemoglobin (Hb) per unit weight. RESULTS Serum prohepcidin levels of HCV positive patients (135±25 ng/mL) were significantly lower than HCV negative patients [148±18 ng/mL, (p=0.025)]. Serum IL-6 levels of HCV positive patients were also significantly lower than HCV negative patients (p=0.016). Serum prohepcidin levels were positively correlated with ferritin (r=0.405, p=0.001) and IL-6 (r=0.271, p=0.050) levels in HD patients. In the HCV positive group, serum prohepcidin levels significantly correlated with ferritin levels (r=0.514 p=0.004). In the HCV negative group, serum prohepcidin levels significantly correlated with serum IL-6 levels (r=0.418, p=0.027). In multiple regression analysis performed to predict prohepcidin in HCV positive patients, serum ferritin was found to be an independent variable (r=0.28, p=0.008). CONCLUSIONS HCV positive HD patients have low levels of serum prohepcidin and IL-6 which might account for iron accumulation together with lower iron and rhuEPO requirements in these patients.