Vitamin K2 Decreases Risk of Liver Cancer in Women With Viral Cirrhosis

Yael Waknine

July 20, 2004

July 20, 2004 — Vitamin K 2 decreases the risk of developing hepatocellular carcinoma in women with viral cirrhosis of the liver, possibly by delaying the onset of carcinogenesis, according to the results of a preliminary study published in the July 21 issue of JAMA.

"A number of findings indicate that vitamin K may play a role in controlling cell growth," write Daiki Habu, MD, PhD, and colleagues, from the Graduate School of Medicine at Osaka City University in Japan. "Geranylgeraniol, which is a side chain of vitamin K 2, strongly induces apoptosis of tumor cells, suggesting that geranylgeraniol might play an important role in inhibiting cell growth."

To determine the effect of vitamin K 2 on the development of hepatocellular carcinoma, the investigators recruited 40 women diagnosed with viral liver cirrhosis, of whom 21 were randomly assigned to treatment with 45 mg per day of vitamin K 2. All patients received symptomatic therapy for ascites and dietary advice.

Compliance in the vitamin K 2 treatment group was good, and no adverse reactions were reported.

During more than seven years of follow-up, the cumulative proportion of patients with hepatocellular carcinoma was significantly smaller in the treatment group (2 of 21 patients) compared with the control group (9 of 19 patients; log-rank test, P = .02). All cases were newly diagnosed and in the initial stages (1 or 2).

Diagnosis of hepatocellular carcinoma was made at 907 days after enrollment in the treatment group compared with 91 days after enrollment in the control group.

Univariate analysis showed the risk ratio for development of hepatocellular carcinoma to be 0.20 in patients given vitamin K 2 compared with the control group (95% confidence interval [CI], 0.04 -0.91; P = .04)

The risk ratio further decreased to 0.13 on multivariate analysis with adjustment for age, alanine aminotransferase activity, serum albumin, total bilirubin, platelet count, α-fetoprotein, and prior treatment with interferon alfa (95% CI, 0.02 - 0.99; P = .05).

The authors note that the annual incidence of hepatocellular carcinoma was 1.6% in the treatment group compared with 8.8% in the control group and 7.9% in the general cirrhotic population.

Limitations of the study include small population size, the exclusion of men from the study, and the participation of only one center.

"[D]espite its small size, our study indicates that vitamin K 2 decreases the risk of hepatocellular carcinoma to about 20% compared with the control group, [and suggests] that vitamin K 2 may delay the onset of hepatocarcinogenesis," the authors write, adding that these preliminary results should be confirmed in multicenter, randomized controlled trials.

This work was supported in part by a grant from Japan's Ministry of Health, Labor, and Welfare.

JAMA. 2004;292:358-361

Reviewed by Gary D. Vogin, MD

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