The effect of menatetrenone, a vitamin K2 analog, on disease recurrence and survival in patients with hepatocellular carcinoma after curative treatment

Abstract

BACKGROUNDThe high recurrence rate of hepatocellular carcinoma (HCC) determines the long‐term prognosis for patients with HCC. In the current study, the authors tested the effects of menatetrenone, a vitamin K2 analog, on recurrent HCC and survival after curative treatment.METHODSSixty‐one patients who were diagnosed as free of HCC after surgical resection or percutaneous local ablation were assigned randomly assigned to either a menatetrenone group (n = 32 patients) or a control group (n = 29 patients). Patients in the menatetrenone group received a daily oral dose of 45 mg of menatetrenone. Disease recurrence and survival rates were analyzed in patients with HCC.RESULTSThe cumulative recurrence rates in the menatetrenone group were 12.5% at 12 months, 39.0% at 24 months, and 64.3% at 36 months; and the corresponding recurrence rates in the control group were 55.2%, 83.2%, and 91.6%, respectively (P = 0.0002). Similar results were obtained even for patients who had low baseline levels of serum des‐γ‐carboxy‐prothrombin. Univariate and multivariate Cox proportional hazard analyses showed that the administration of menatetrenone was the only factor related to the recurrence rate of HCC. The cumulative survival rates for the patients who received menatetrenone were 100% at 12 months, 96.6% at 24 months, and 87.0% at 36 months; and the corresponding survival rates for patients in the control group were 96.4%, 80.9%, and 64.0%, respectively (P = 0.051).CONCLUSIONSThe current study findings suggested that menatetrenone may have a suppressive effect on recurrence of HCC and a beneficial effect on survival, although a larger, placebo‐controlled trial will be required to prove these effects. Cancer 2006. © 2006 American Cancer Society.

Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma

“…The safety, relatively low cost, and ease of use make vitamin K 2 a suitable candidate for clinical trials that assess the value of combination of chemoprevention or chemotherapy in at-risk patients or in patients with a confirmed diagnosis of HCC [116,[122][123][124][125].…”

“…Vitamin K 2 was reported to inhibit HCC development among female patients with cirrhosis, who had received the vitamin for the prevention of osteoporosis [122]. A small RCT suggested that vitamin K 2 was effective in suppressing HCC recurrence and may improve survival [124]. However, subsequent, large-scale RCT met with an early termination because of lacking evidence of effects.…”

“…A pilot study by Mizuta et al [124] on HCC patients who had undergone either percutaneous local ablation or surgery suggested that menatetrenone, a vitamin K 2 analogue, may have a suppressive effect on the recurrence of HCC and a beneficial effect on survival.…”

Selective chemiluminescence method for monitoring of vitamin K homologues in rheumatoid arthritis patients

“…The importance of vitamin K in bone metabolism is further supported by studies showing that vitamin K inhibits osteoclastic bone resorption by induction of osteoclast apoptosis [13,14]. In addition to these biological activities, vitamin K 2 has been reported to induce apoptosis in hepatocellular carcinoma, leukaemia [15] and myelodysplastic syndrome cell lines [16].…”

Vitamin K2 augments 5-fluorouracil-induced growth inhibition of human hepatocellular carcinoma cells by inhibiting NF-κB activation

“…Recently VK2 also was found to inhibit hepatoma cell invasiveness and metastasis (11). More importantly, we recently demonstrated that administration of VK2 to HCC patients significantly decreased recurrence of HCC after curative local ablation therapy (12). Habu et al (13) reported that VK2 suppressed development of HCC from the cirrhotic liver in patients infected with hepatitis virus.…”