title: Effect of vitamin K2 on the recurrence of hepatocellular carcinoma.
abstract: Hepatocellular carcinoma (HCC) is characterized by frequent recurrence, even after curative treatment. Vitamin K2, which has been reported to reduce HCC development, may be effective in preventing HCC recurrence. Patients who underwent curative ablation or resection of HCC were randomly assigned to receive placebo, 45 mg/day, or 90 mg/day vitamin K2 in double-blind fashion. HCC recurrence was surveyed every 12 weeks with dynamic computed tomography/magnetic resonance imaging, with HCC-specific tumor markers monitored every 4 weeks. The primary aim was to confirm the superiority of active drug to placebo concerning disease-free survival (DFS), and the secondary aim was to evaluate dose-response relationship. Disease occurrence and death from any cause were treated as events. Hazard ratios (HRs) for disease occurrence and death were calculated using a Cox proportional hazards model. Enrollment was commenced in March 2004. DFS was assessed in 548 patients, including 181 in the placebo group, 182 in the 45-mg/day group, and 185 in the 90-mg/day group. Disease occurrence or death was diagnosed in 58, 52, and 76 patients in the respective groups. The second interim analysis indicated that vitamin K2 did not prevent disease occurrence or death, with an HR of 1.150 (95% confidence interval: 0.843-1.570, one-sided; P=0.811) between the placebo and combined active-drug groups, and the study was discontinued in March 2007.
  
  
  CONCLUSIONS
  Efficacy of vitamin K2 in suppressing HCC recurrence was not confirmed in this double-blind, randomized, placebo-controlled study.
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, and Department of Gastroenterology and Hepatology, Kanto Central Hospital, Tokyo, Japan. yoshida-2im@h.u-tokyo.ac.jp
authors.forename: Haruhiko
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authors.lastname: Yoshida
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Shiratori
authors.forename: Masatoshi
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authors.lastname: Kudo
authors.forename: Shuichiro
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authors.lastname: Shiina
authors.forename: Toshihiko
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authors.lastname: Mizuta
authors.forename: Masamichi
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authors.lastname: Kojiro
authors.forename: Kyosuke
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authors.lastname: Yamamoto
authors.forename: Yukihiro
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authors.lastname: Koike
authors.forename: Kenichi
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authors.lastname: Saito
authors.forename: Nozomu
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authors.lastname: Koyanagi
authors.forename: Takao
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authors.lastname: Kawabe
authors.forename: Seiji
authors.initials: S
authors.lastname: Kawazoe
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Kobashi
authors.forename: Hiroshi
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authors.lastname: Kasugai
authors.forename: Yukio
authors.initials: Y
authors.lastname: Osaki
authors.forename: Yasuyuki
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authors.lastname: Araki
authors.forename: Namiki
authors.initials: N
authors.lastname: Izumi
authors.forename: Hiroko
authors.initials: H
authors.lastname: Oka
authors.forename: Kunihiko
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authors.lastname: Tsuji
authors.forename: Joji
authors.initials: J
authors.lastname: Toyota
authors.forename: Toshihito
authors.initials: T
authors.lastname: Seki
authors.forename: Toshiya
authors.initials: T
authors.lastname: Osawa
authors.forename: Naohiko
authors.initials: N
authors.lastname: Masaki
authors.forename: Masao
authors.initials: M
authors.lastname: Ichinose
authors.forename: Masataka
authors.initials: M
authors.lastname: Seike
authors.forename: Akihisa
authors.initials: A
authors.lastname: Ishikawa
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Ueno
authors.forename: Kazumi
authors.initials: K
authors.lastname: Tagawa
authors.forename: Ryoko
authors.initials: R
authors.lastname: Kuromatsu
authors.forename: Shotaro
authors.initials: S
authors.lastname: Sakisaka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ikeda
authors.forename: Hidekatsu
authors.initials: H
authors.lastname: Kuroda
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kokuryu
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Yamashita
authors.forename: Isao
authors.initials: I
authors.lastname: Sakaida
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Katamoto
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kikuchi
authors.forename: Minoru
authors.initials: M
authors.lastname: Nomoto
authors.forename: Masao
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authors.lastname: Omata
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000517:prevention & control* / Q000601:surgery; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000517:prevention & control* / Q000601:surgery; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D024482:Vitamin K 2 / Q000627:therapeutic use*; D014815:Vitamins / Q000627:therapeutic use*
chemical_list: D014815:Vitamins; D024482:Vitamin K 2