%0 Journal Article
%T Pathogenic Role of Iron Deposition in Reticuloendothelial Cells during the Development of Chronic Hepatitis C
%A Hironori Mitsuyoshi
%A Kohichiroh Yasui
%A Kanji Yamaguchi
%A Masahito Minami
%A Takeshi Okanoue
%A Yoshito Itoh
%J International Journal of Hepatology
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/686420
%X Aim. Chronic hepatitis C (CHepC) is frequently associated with hepatic iron overload, yet mechanisms underlying iron-induced liver injury have not been elucidated. We examined the significance of iron deposition in hepatocytes (HC) and reticuloendothelial cells (REC) in CHepC. Methods. Stainable hepatic iron was scored according to the iron deposition pattern in 373 patients. The levels of serum soluble TNF-¦Á receptor (sTNFR2) and hepatic hepcidin mRNA and the efficacy of phlebotomy were compared among patients with different iron deposition patterns. Results. Serum transaminase levels and hepatic scores of stage, grade, and steatosis were higher in patients with REC iron staining than in those without. REC iron scores were independently associated with advanced stage. Serum sTNFR2 levels were significantly higher in patients with REC iron than in those without. REC iron scores were independently correlated with sTNFR2 levels. Compared with patients without stainable iron, those with iron overload had decreased ratios of hepcidin mRNA to serum ferritin. The efficacy of phlebotomy was greater in patients with REC iron than in those without REC iron. Conclusions. The present results show the importance of REC iron for the development of CHepC and the therapeutic effect of phlebotomy in CHepC. 1. Introduction Chronic hepatitis C (CHepC) is frequently associated with hepatic iron overload [1¨C3]. Elevation of serum iron indices or stainable hepatic iron has been shown in 40 to 70% of patients with CHepC [1¨C3]. From these observations, iron-induced oxidative stress has been considered to be an underlying mechanism of liver injury and of development of hepatocellular carcinoma [4¨C6]. The mechanisms of hepatic iron overload in CHepC have not yet been elucidated. However, hepcidin has attracted much attention as an important factor in the disease process. Hepcidin is exclusively produced in the liver and regulates body iron stores [7, 8]. Hepcidin causes internalization and degradation of iron-transporter ferroportin on duodenal enterocytes and macrophages, thereby blocking iron absorption and iron recycling, respectively [9]. In hereditary hemochromatosis (HH), defective hepcidin synthesis results in a subsequent increase in body iron stores [10]. In CHepC, hepatic iron overload has been attributed to the mutation of the hemochromatosis protein (HFE) gene [11], since several reports have found an association between HFE genotypes and iron overload in patients with CHepC [12¨C14]. Another possible mechanism is the direct effect of the hepatitis C virus (HCV) on
%U http://www.hindawi.com/journals/ijh/2013/686420/