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Daiki Habu, MD, PhD; Susumu Shiomi, MD, PhD; Akihiro Tamori, MD, PhD; Tadashi Takeda, MD, PhD; Takashi Tanaka, MD, PhD; Shoji Kubo, MD, PhD; Shuhei Nishiguchi, MD, PhD

JAMA. 2004;292:358-361.

Context  Previous findings indicate that vitamin K₂ (menaquinone) may play a role in controlling cell growth.

Objective  To determine whether vitamin K₂has 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, -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.

Author Affiliations: Departments of Hepatology (Drs Habu, Tamori, Takeda, and Nishiguchi), Nuclear Medicine (Dr Shiomi), Public Health (Dr Tanaka), and Surgery (Dr Kubo), Graduate School of Medicine, Osaka City University, Osaka, Japan.

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RELATED LETTERS

Vitamin K Deficiency and Hepatocellular Carcinoma
Marie-Astrid Piquet, Isabelle Hourmand-Ollivier, and Thông Dao
JAMA. 2004;292(21):2580-2581.
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Vitamin K Deficiency and Hepatocellular Carcinoma—Reply
Daiki Habu, Susumu Shiomi, Takashi Tanaka, and Shuhei Nishiguchi
JAMA. 2004;292(21):2581.
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