Preventive effects of vitamin K on recurrent disease in patients with hepatocellular carcinoma arising from hepatitis C viral infection

J Gastroenterol Hepatol. 2007 Apr;22(4):518-22. doi: 10.1111/j.1440-1746.2007.04844.x.


Background: Despite the progression of therapeutic approaches, a high frequency of recurrence is what determines the long-term prognosis of patients with hepatocellular carcinoma (HCC). In this study, the chemopreventive effects of vitamin K2 on the recurrence and survival of patients with HCC after curative therapy were evaluated.

Methods: Sixty patients who were diagnosed to be free of HCC after radiofrequency ablation therapy or surgery were randomly assigned to either the vitamin K2 group (n = 30 patients) or the control group (n = 30 patients). All patients were positive for the hepatitis C virus (HCV) antibody and hepatitis B surface antigen positive patients were excluded from this study. Patients in the vitamin K2 group received an oral dose of menatetrenone at 45 mg per day. Disease recurrence and the survival rates were analyzed in patients with HCC.

Results: The cumulative recurrence-free rates in the vitamin K2 group were 92.3% at 12 months, 48.6% at 24 months and 38.8% at 36 months; and those in the control group were 71.7%, 35.9% and 9.9%, respectively (P = 0.045). The cumulative survival rates in the vitamin K2 group were 100% at 12 months, 95.0% at 24 months and 77.5% at 36 months; and those in the control group were 95.8%, 90.2% and 66.4%, respectively (P = 0.70).

Conclusions: Vitamin K2 may have a suppressive effect on the recurrence of HCC and a beneficial effect on tumor recurrence. However, there was no significant difference in the survival rates. The chemopreventive effects of vitamin K2 are not sufficient. The development of a further regimen such as combination therapy is required.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Carcinoma, Hepatocellular / prevention & control*
  • Carcinoma, Hepatocellular / surgery
  • Carcinoma, Hepatocellular / therapy
  • Catheter Ablation
  • Female
  • Hepatitis C Antibodies / analysis
  • Humans
  • Liver Neoplasms / prevention & control*
  • Liver Neoplasms / surgery
  • Liver Neoplasms / therapy
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Secondary Prevention
  • Survival Rate
  • Vitamin K 2 / analogs & derivatives*
  • Vitamin K 2 / therapeutic use


  • Hepatitis C Antibodies
  • Vitamin K 2
  • menatetrenone