Vitamin K2 Supplementation and Clinical Outcomes in Hepatocellular Carcinoma Patients: A Meta-Analysis with Trial Sequential Analysis.

[BACKGROUND AND AIMS] Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality globally. The potential benefits of vitamin K (VK) supplementation for patients with HCC remain unclear. This study aimed to evaluate the impact of VK supplementation on clinical outcomes in patients undergoing HCC treatment.

[METHODS] A systematic search across Medline, Scopus, and Web of Science databases identified relevant studies. Pooled odds ratios (OR) with 95% confidence intervals (CI) assessed treatment group differences in binary outcomes. Heterogeneity was evaluated using statistics. Analyses were performed using R (version 4.2.3).

[RESULTS] Eleven studies encompassing 1,030 patients were included. VK supplementation significantly reduced disease recurrence (DR) compared to control at 1 year (OR 0.55, 95% CI 0.32-0.97;  = 0.039), 2 years (OR 0.52, 95% CI 0.35-0.77;  = 0.001), and 3 years (OR 0.41, 95% CI 0.25-0.67;  = 0.000). Additionally, VK supplementation significantly decreased mortality at 1 year (OR 0.20, 95% CI 0.07-0.60;  = 0.004), 2 years (OR 0.38, 95% CI 0.18-0.82;  = 0.014), and 3 years (OR 0.37, 95% CI 0.21-0.66;  = 0.001). Notably, no significant difference in adverse events was observed between VK and control groups (OR 3.56, 95% CI 0.06-198.66;  = 0.536).

[CONCLUSION] This study suggests substantial benefits associated with VK supplementation in HCC patients, particularly in reducing DR and mortality across one, two, and three years. Importantly, these improvements were achieved without a significant increase in adverse events, indicating good tolerability of VK supplementation in this population.