Evaluation of liver hepcidin mRNA expression in patients with chronic hepatitis C virus infection [HCV] and liver cirrhosis

ABSTRACT

Elevated serum ferritin and iron accumulation in the liver are common in patients with chronic hepatitis C virus infection and have been associated with more aggressive disease and decreased response to interferon therapy, but the mechanism is unknown. Recently identified hepcidin, which is a small cysteine-rich cationic peptide produced by hepatocytes, secreted into plasma and excreted in urine, acts as regulator of intestinal iron absorption and iron recycling by the macrophage. This study was conducted to evaluate hepatic hepcidin mRNA expression in patients with chronic HCV infection and correlate its expression level with serum iron, serum ferritin and the grading and staging of liver disease. Fifty patients [40 males and 10 females] with chronic HCV infection were classified into two groups, chronic hepatitis [CH, n = 35, 28 males and 7 females] and liver cirrhosis [LC, n = 15, 12 males and 3 females]. In addition, 18 apparently healthy subjects [donors for partial liver transplantation] served as the control group. All patients were both anti-HCV and HCV RNA positive. Serum iron and serum ferritin were measured for all studied groups. Hepatic hepcidin mRNA expression level was determined by SYBR-green real-time PCR. Serum iron and ferritin were significantly higher in the patient groups compared to control group [p <0.001]. Hepatic hepcidin mRNA expression was significantly decreased in the patient groups than in the control group [p <0.001]. Also its expression was decreased in patients with liver cirrhosis than in patients with chronic hepatitis. There was a negative correlation between hepatic hepcidin mRNA and serum iron and ferritin in the patient groups. On the other hand no correlation was detected between it and histological grading of activity [r = -0.001, p >0.05]. Meanwhile there was a strong negative correlation between hepatic hepcidin mRNA and the histological stage of fibrosis [r = -0.51, p <0.001]. In conclusion failure of homeostatic regulation of hepatic hepcidin expression may be induced by HCV infection and this may cause elevation of serum iron and ferritin levels in patients with HCV infection. Therefore, understanding the role of the liver in hepcidin regulation and iron homeostasis may be helpful in the management of HCV hepatitis