title: Hepcidin/ferroportin expression levels involve efficacy of pegylated-interferon plus ribavirin in hepatitis C virus-infected liver.
abstract: OBJECTIVE
  To investigate the relationship between the iron-metabolism-related gene expression profiles and efficacy of antiviral therapy in chronic hepatitis C patients.
  
  
  METHODS
  The hepatic expression profile of iron-metabolism-related genes was analyzed and its association with virological response to pegylated-interferon plus ribavirin combination therapy was evaluated. A hundred patients with chronic hepatitis C (genotype1b, n = 50; genotype 2, n = 50) were enrolled and retrospectively analyzed. Liver biopsy samples were subjected to quantitative polymerase chain reaction for iron-metabolism-related genes and protein expression (Western blotting analysis) for ferroportin. As a control, normal liver tissue was obtained from 18 living donors of liver transplantation. Serum hepcidin level was measured by sensitive liquid chromatography/electrospray ionization tandem mass spectrometry.
  
  
  RESULTS
  Iron overload is associated with liver damage by increasing oxidative stress and hepatitis C virus (HCV) is reported to induce iron accumulation in hepatocytes in vivo. Conversely, iron administration suppresses HCV replication in vitro. Therefore, the association between HCV infection and iron metabolism remains unclear. Compared with controls, patients had significantly higher gene expression for transferrin, iron-regulatory proteins 1 and 2, divalent metal transporter 1, and ferroportin, but similar for transferrin receptors 1 and 2, and hepcidin. When the expression profiles were compared between sustained virological response (SVR) and non-SVR patients, the former showed significantly lower transcription and protein expression of hepcidin and ferroportin. Expression of hepcidin-regulating genes, BMPR1, BMPR2, and hemojuvelin, was significantly increased, whereas BMP2 was decreased in HCV-infected liver. BMPR2 and hemojuvelin expression was significantly lower in the SVR than non-SVR group. HCV infection affects the expression of iron-metabolism-related genes, leading to iron accumulation in hepatocytes.
  
  
  CONCLUSIONS
  Decreased expression of hepcidin and ferroportin in SVR patients indicates the importance of hepatocytic iron retention for viral response during pegylated-interferon plus ribavirin treatment.
authors: Motoyuki Kohjima, Tsuyoshi Yoshimoto, Nobuyoshi Fukushima, Kunitaka Fukuizumi, Tsukasa Nakamura, Miho Kurokawa, Nao Fujimori, Ken Kawabe, Kazuhiro Haraguchi, Yorinobu Sumida, Naohiko Harada, Makoto Nakamuta, Department of Gastroenterology and Clinical Research Center, National Hospital Organization Kyushu Medical Center, Fukuoka 810-8563, Japan.
authors: Motoyuki
authors: M
authors: Kohjima
authors: Motoyuki Kohjima, Tsuyoshi Yoshimoto, Nobuyoshi Fukushima, Kunitaka Fukuizumi, Tsukasa Nakamura, Miho Kurokawa, Nao Fujimori, Ken Kawabe, Kazuhiro Haraguchi, Yorinobu Sumida, Naohiko Harada, Makoto Nakamuta, Department of Gastroenterology and Clinical Research Center, National Hospital Organization Kyushu Medical Center, Fukuoka 810-8563, Japan.
authors: Tsuyoshi
authors: T
authors: Yoshimoto
authors: Motoyuki Kohjima, Tsuyoshi Yoshimoto, Nobuyoshi Fukushima, Kunitaka Fukuizumi, Tsukasa Nakamura, Miho Kurokawa, Nao Fujimori, Ken Kawabe, Kazuhiro Haraguchi, Yorinobu Sumida, Naohiko Harada, Makoto Nakamuta, Department of Gastroenterology and Clinical Research Center, National Hospital Organization Kyushu Medical Center, Fukuoka 810-8563, Japan.
authors: Munechika
authors: M
authors: Enjoji
authors: Motoyuki Kohjima, Tsuyoshi Yoshimoto, Nobuyoshi Fukushima, Kunitaka Fukuizumi, Tsukasa Nakamura, Miho Kurokawa, Nao Fujimori, Ken Kawabe, Kazuhiro Haraguchi, Yorinobu Sumida, Naohiko Harada, Makoto Nakamuta, Department of Gastroenterology and Clinical Research Center, National Hospital Organization Kyushu Medical Center, Fukuoka 810-8563, Japan.
authors: Nobuyoshi
authors: N
authors: Fukushima
authors: Motoyuki Kohjima, Tsuyoshi Yoshimoto, Nobuyoshi Fukushima, Kunitaka Fukuizumi, Tsukasa Nakamura, Miho Kurokawa, Nao Fujimori, Ken Kawabe, Kazuhiro Haraguchi, Yorinobu Sumida, Naohiko Harada, Makoto Nakamuta, Department of Gastroenterology and Clinical Research Center, National Hospital Organization Kyushu Medical Center, Fukuoka 810-8563, Japan.
authors: Kunitaka
authors: K
authors: Fukuizumi
authors: Motoyuki Kohjima, Tsuyoshi Yoshimoto, Nobuyoshi Fukushima, Kunitaka Fukuizumi, Tsukasa Nakamura, Miho Kurokawa, Nao Fujimori, Ken Kawabe, Kazuhiro Haraguchi, Yorinobu Sumida, Naohiko Harada, Makoto Nakamuta, Department of Gastroenterology and Clinical Research Center, National Hospital Organization Kyushu Medical Center, Fukuoka 810-8563, Japan.
authors: Tsukasa
authors: T
authors: Nakamura
authors: Motoyuki Kohjima, Tsuyoshi Yoshimoto, Nobuyoshi Fukushima, Kunitaka Fukuizumi, Tsukasa Nakamura, Miho Kurokawa, Nao Fujimori, Ken Kawabe, Kazuhiro Haraguchi, Yorinobu Sumida, Naohiko Harada, Makoto Nakamuta, Department of Gastroenterology and Clinical Research Center, National Hospital Organization Kyushu Medical Center, Fukuoka 810-8563, Japan.
authors: Miho
authors: M
authors: Kurokawa
authors: Motoyuki Kohjima, Tsuyoshi Yoshimoto, Nobuyoshi Fukushima, Kunitaka Fukuizumi, Tsukasa Nakamura, Miho Kurokawa, Nao Fujimori, Ken Kawabe, Kazuhiro Haraguchi, Yorinobu Sumida, Naohiko Harada, Makoto Nakamuta, Department of Gastroenterology and Clinical Research Center, National Hospital Organization Kyushu Medical Center, Fukuoka 810-8563, Japan.
authors: Nao
authors: N
authors: Fujimori
authors: Motoyuki Kohjima, Tsuyoshi Yoshimoto, Nobuyoshi Fukushima, Kunitaka Fukuizumi, Tsukasa Nakamura, Miho Kurokawa, Nao Fujimori, Ken Kawabe, Kazuhiro Haraguchi, Yorinobu Sumida, Naohiko Harada, Makoto Nakamuta, Department of Gastroenterology and Clinical Research Center, National Hospital Organization Kyushu Medical Center, Fukuoka 810-8563, Japan.
authors: Yusuke
authors: Y
authors: Sasaki
authors: Motoyuki Kohjima, Tsuyoshi Yoshimoto, Nobuyoshi Fukushima, Kunitaka Fukuizumi, Tsukasa Nakamura, Miho Kurokawa, Nao Fujimori, Ken Kawabe, Kazuhiro Haraguchi, Yorinobu Sumida, Naohiko Harada, Makoto Nakamuta, Department of Gastroenterology and Clinical Research Center, National Hospital Organization Kyushu Medical Center, Fukuoka 810-8563, Japan.
authors: Yasushi
authors: Y
authors: Shimonaka
authors: Motoyuki Kohjima, Tsuyoshi Yoshimoto, Nobuyoshi Fukushima, Kunitaka Fukuizumi, Tsukasa Nakamura, Miho Kurokawa, Nao Fujimori, Ken Kawabe, Kazuhiro Haraguchi, Yorinobu Sumida, Naohiko Harada, Makoto Nakamuta, Department of Gastroenterology and Clinical Research Center, National Hospital Organization Kyushu Medical Center, Fukuoka 810-8563, Japan.
authors: Yusuke
authors: Y
authors: Murata
authors: Motoyuki Kohjima, Tsuyoshi Yoshimoto, Nobuyoshi Fukushima, Kunitaka Fukuizumi, Tsukasa Nakamura, Miho Kurokawa, Nao Fujimori, Ken Kawabe, Kazuhiro Haraguchi, Yorinobu Sumida, Naohiko Harada, Makoto Nakamuta, Department of Gastroenterology and Clinical Research Center, National Hospital Organization Kyushu Medical Center, Fukuoka 810-8563, Japan.
authors: Susumu
authors: S
authors: Koyama
authors: Motoyuki Kohjima, Tsuyoshi Yoshimoto, Nobuyoshi Fukushima, Kunitaka Fukuizumi, Tsukasa Nakamura, Miho Kurokawa, Nao Fujimori, Ken Kawabe, Kazuhiro Haraguchi, Yorinobu Sumida, Naohiko Harada, Makoto Nakamuta, Department of Gastroenterology and Clinical Research Center, National Hospital Organization Kyushu Medical Center, Fukuoka 810-8563, Japan.
authors: Ken
authors: K
authors: Kawabe
authors: Motoyuki Kohjima, Tsuyoshi Yoshimoto, Nobuyoshi Fukushima, Kunitaka Fukuizumi, Tsukasa Nakamura, Miho Kurokawa, Nao Fujimori, Ken Kawabe, Kazuhiro Haraguchi, Yorinobu Sumida, Naohiko Harada, Makoto Nakamuta, Department of Gastroenterology and Clinical Research Center, National Hospital Organization Kyushu Medical Center, Fukuoka 810-8563, Japan.
authors: Kazuhiro
authors: K
authors: Haraguchi
authors: Motoyuki Kohjima, Tsuyoshi Yoshimoto, Nobuyoshi Fukushima, Kunitaka Fukuizumi, Tsukasa Nakamura, Miho Kurokawa, Nao Fujimori, Ken Kawabe, Kazuhiro Haraguchi, Yorinobu Sumida, Naohiko Harada, Makoto Nakamuta, Department of Gastroenterology and Clinical Research Center, National Hospital Organization Kyushu Medical Center, Fukuoka 810-8563, Japan.
authors: Yorinobu
authors: Y
authors: Sumida
authors: Motoyuki Kohjima, Tsuyoshi Yoshimoto, Nobuyoshi Fukushima, Kunitaka Fukuizumi, Tsukasa Nakamura, Miho Kurokawa, Nao Fujimori, Ken Kawabe, Kazuhiro Haraguchi, Yorinobu Sumida, Naohiko Harada, Makoto Nakamuta, Department of Gastroenterology and Clinical Research Center, National Hospital Organization Kyushu Medical Center, Fukuoka 810-8563, Japan.
authors: Naohiko
authors: N
authors: Harada
authors: Motoyuki Kohjima, Tsuyoshi Yoshimoto, Nobuyoshi Fukushima, Kunitaka Fukuizumi, Tsukasa Nakamura, Miho Kurokawa, Nao Fujimori, Ken Kawabe, Kazuhiro Haraguchi, Yorinobu Sumida, Naohiko Harada, Makoto Nakamuta, Department of Gastroenterology and Clinical Research Center, National Hospital Organization Kyushu Medical Center, Fukuoka 810-8563, Japan.
authors: Masaki
authors: M
authors: Kato
authors: Motoyuki Kohjima, Tsuyoshi Yoshimoto, Nobuyoshi Fukushima, Kunitaka Fukuizumi, Tsukasa Nakamura, Miho Kurokawa, Nao Fujimori, Ken Kawabe, Kazuhiro Haraguchi, Yorinobu Sumida, Naohiko Harada, Makoto Nakamuta, Department of Gastroenterology and Clinical Research Center, National Hospital Organization Kyushu Medical Center, Fukuoka 810-8563, Japan.
authors: Kazuhiro
authors: K
authors: Kotoh
authors: Motoyuki Kohjima, Tsuyoshi Yoshimoto, Nobuyoshi Fukushima, Kunitaka Fukuizumi, Tsukasa Nakamura, Miho Kurokawa, Nao Fujimori, Ken Kawabe, Kazuhiro Haraguchi, Yorinobu Sumida, Naohiko Harada, Makoto Nakamuta, Department of Gastroenterology and Clinical Research Center, National Hospital Organization Kyushu Medical Center, Fukuoka 810-8563, Japan.
authors: Makoto
authors: M
authors: Nakamuta
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D015153:Blotting, Western; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D002853:Chromatography, Liquid; D004359:Drug Therapy, Combination; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D064451:Hepcidins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000821:virology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use*; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry; D013997:Time Factors; D016896:Treatment Outcome; D000098742:Ferroportin
chemical_list: D000998:Antiviral Agents; D027682:Cation Transport Proteins; C578702:HAMP protein, human; D064451:Hepcidins; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D000098742:Ferroportin; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a
keywords: Chronic hepatitis C; Ferroportin; Hepcidin; Interferon; Iron-metabolism