title: Impact of serum ferritin level on hepatocarcinogenesis in chronic hepatitis C patients.
abstract: OBJECTIVE
  To elucidate the impact of the serum ferritin level, a surrogate indicator of hepatic iron accumulation, on hepatocarcinogenesis in chronic hepatitis C patients.
  
  
  METHODS
  Serum ferritin was measured in 487 chronic hepatitis C patients without history of hepatocellular carcinoma (HCC) after excluding patients in phlebotomy, those with overt chronic gastrointestinal bleeding and those who achieved sustained virological response before enrollment. Patients were divided into four groups (G1-G4) by quartile points of serum ferritin, with sexes separated.
  
  
  RESULTS
  The serum ferritin level was positively correlated with total bilirubin, aspartate aminotransferase, alanine aminotransferase (ALT), γ-glutamyltransferase, hemoglobin and AFP, and inversely correlated with prothrombin activity in both sexes. A significant difference in HCC incidence was observed only in male patients; the incidence was higher in G1 (≤80 ng/mL, n = 54) and G4 (≥323 ng/mL, n = 54) compared with that of G2 (81-160 ng/mL, n = 54) and G3 (161-322 ng/mL, n = 52). The spline curve indicating the relationship between the hazard ratio and serum ferritin level took the form of a J-shape for male patients. In multivariate analysis, G1 and G4 showed higher incidence of HCC among men with a hazard ratio of 2.19 (95% confidence interval, 1.02-4.70; P = 0.045) compared with G2 and G3, together with older age, lower serum albumin and ALT above the normal upper limit.
  
  
  CONCLUSIONS
  The serum ferritin level is an independent risk factor for HCC development in male patients with chronic hepatitis C when the level is extremely high or low.
authors: Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors: Koji
authors: K
authors: Uchino
authors: Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors: Ryosuke
authors: R
authors: Tateishi
authors: Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors: Naoto
authors: N
authors: Fujiwara
authors: Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors: Tatsuya
authors: T
authors: Minami
authors: Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors: Masaya
authors: M
authors: Sato
authors: Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors: Kenichiro
authors: K
authors: Enooku
authors: Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors: Hayato
authors: H
authors: Nakagawa
authors: Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors: Yoshinari
authors: Y
authors: Asaoka
authors: Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors: Yuji
authors: Y
authors: Kondo
authors: Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors: Haruhiko
authors: H
authors: Yoshida
authors: Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors: Kyoji
authors: K
authors: Moriya
authors: Department of Gastroenterology, Juntendo University, Tokyo, Japan.
authors: Shuichiro
authors: S
authors: Shiina
authors: Yamanashi Prefectural Hospital Organization, Yamanashi, Japan.
authors: Masao
authors: M
authors: Omata
authors: Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors: Kazuhiko
authors: K
authors: Koike
keywords: hepatocellular carcinoma; iron metabolism; liver; oxidative stress; risk factor