Role of Vitamin K2 in the Development of Hepatocellular Carcinoma in Women With Viral Cirrhosis of the Liver

CONTEXT: Previous findings indicate that vitamin K2 (menaquinone) may play a role in controlling cell growth. OBJECTIVE: To determine whether vitamin K2 has preventive effects on the development of hepatocellular carcinoma in women with viral cirrhosis of the liver. DESIGN, SETTING, AND PARTICIPANTS: Forty women diagnosed as having viral liver cirrhosis were admitted to a university hospital between 1996 and 1998 and were randomly assigned to the treatment or control group. The original goal of the trial was to assess the long-term effects of vitamin K2 on bone loss in women with viral liver cirrhosis. However, study participants also satisfied criteria required for examination of the effects of such treatment on the development of hepatocellular carcinoma. INTERVENTIONS: The treatment group received 45 mg/d of vitamin K2 (n = 21). Participants in the treatment and control groups received symptomatic therapy to treat ascites, if necessary, and dietary advice. MAIN OUTCOME MEASURE: Cumulative proportion of patients with hepatocellular carcinoma. RESULTS: Hepatocellular carcinoma was detected in 2 of the 21 women given vitamin K2 and 9 of the 19 women in the control group. The cumulative proportion of patients with hepatocellular carcinoma was smaller in the treatment group (log-rank test, P =.02). On univariate analysis, the risk ratio for the development of hepatocellular carcinoma in the treatment group compared with the control group was 0.20 (95% confidence interval CI, 0.04-0.91; P =.04). On multivariate analysis with adjustment for age, alanine aminotransferase activity, serum albumin, total bilirubin, platelet count, alpha-fetoprotein, and history of treatment with interferon alfa, the risk ratio for the development of hepatocellular carcinoma in patients given vitamin K2 was 0.13 (95% CI, 0.02-0.99; P =.05). CONCLUSION: There is a possible role for vitamin K2 in the prevention of hepatocellular carcinoma in women with viral cirrhosis.