title: Pathogenic Role of Iron Deposition in Reticuloendothelial Cells during the Development of Chronic Hepatitis C.
abstract: 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- α 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.
authors: Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi Hirokouji, Kamigyo-ku, Kyoto 602-8566, Osaka 564-0013, Japan.
authors: Hironori
authors: H
authors: Mitsuyoshi
authors: Kohichiroh
authors: K
authors: Yasui
authors: Kanji
authors: K
authors: Yamaguchi
authors: Masahito
authors: M
authors: Minami
authors: Takeshi
authors: T
authors: Okanoue
authors: Yoshito
authors: Y
authors: Itoh
references: Am J Gastroenterol. 1999 May;94(5):1332-40
references: 10235215
references: Am J Physiol. 1998 Sep;275(3):G387-92
references: 9724248
references: Gastroenterology. 1999 Jan;116(1):127-34
references: 9869610
references: Blood. 2006 Jan 1;107(1):328-33
references: 16141345
references: Alcohol Clin Exp Res. 2005 Nov;29(11 Suppl):189S-93S
references: 16344607
references: Hepatology. 1999 Oct;30(4):987-96
references: 10498651
references: Gastroenterology. 2003 May;124(5):1509-23
references: 12730889
references: Biochem Genet. 1999 Feb;37(1-2):63-8
references: 10429833
references: Gastroenterology. 1992 Jun;102(6):2108-13
references: 1587431
references: J Hepatol. 1999 Dec;31(6):979-84
references: 10604569
references: Gastroenterology. 2003 Feb;124(2):318-26
references: 12557137
references: J Clin Invest. 1992 Aug;90(2):533-6
references: 1322942
references: Cell Metab. 2008 Apr;7(4):288-90
references: 18396134
references: J Clin Invest. 1995 Apr;95(4):1824-31
references: 7706489
references: Autoimmun Rev. 2012 Oct;11(12):883-9
references: 22449938
references: J Biol Chem. 2001 Mar 16;276(11):7806-10
references: 11113131
references: Gastroenterology. 2006 Jun;130(7):2229-34
references: 16762645
references: Cell. 2004 Apr 30;117(3):285-97
references: 15109490
references: J Gastroenterol. 2007 Oct;42(10):830-6
references: 17940836
references: Am J Clin Pathol. 2000 Apr;113(4):546-54
references: 10761457
references: J Clin Microbiol. 1997 Jan;35(1):201-7
references: 8968908
references: Gastroenterology. 2008 Jan;134(1):226-38
references: 18166355
references: Semin Liver Dis. 2005 Nov;25(4):392-401
references: 16315133
references: Hepatology. 2011 Feb;53(2):448-57
references: 21274866
references: Am J Gastroenterol. 1996 Jul;91(7):1367-73
references: 8677997
references: J Hepatol. 2002 Dec;37(6):848-54
references: 12445428
references: Mol Med. 2007 Jan-Feb;13(1-2):97-104
references: 17515961
references: Am J Physiol Gastrointest Liver Physiol. 2006 May;290(5):G847-51
references: 16603728
references: Virology. 1993 Feb;192(2):430-7
references: 7678473
references: Semin Diagn Pathol. 1998 Nov;15(4):237-45
references: 9845425