Effect of Vitamin K2 on the Recurrence of Hepatocellular Carcinoma
Effect of Vitamin K2 on the Recurrence of Hepatocellular Carcinoma
复制标题
DOI：
10.1002/hep.24430
复制
发表时间：
2011-08-01
期刊：
影响因子：
13.5
通讯作者：
Omata, Masao
中科院分区：
文献类型：
--
作者：
Yoshida, Haruhiko;Shiratori, Yasushi;Omata, Masao
肝细胞癌 (HCC) 的特点是频繁复发，即使经过治愈性治疗也是如此。据报道，维生素 K2 可以减少 HCC 的发展，可能有效预防 HCC 复发。接受 HCC 根治性消融或切除术的患者被随机分配接受安慰剂、45 毫克/天或 90 毫克/天的双盲维生素 K2 治疗。每 12 周使用动态计算机断层扫描/磁共振成像调查一次 HCC 复发情况，每 4 周监测一次 HCC 特异性肿瘤标志物。主要目的是确认活性药物在无病生存（DFS）方面相对于安慰剂的优越性，次要目的是评估剂量-反应关系。疾病的发生和任何原因造成的死亡都被视为事件。使用 Cox 比例风险模型计算疾病发生和死亡的风险比 (HR)。招募工作于 2004 年 3 月开始。对 548 名患者进行了 DFS 评估，其中安慰剂组 181 名，45 毫克/天组 182 名，90 毫克/天组 185 名。各组中分别有 58 例、52 例和 76 例患者被诊断出疾病发生或死亡。第二次中期分析表明，维生素 K2 不能预防疾病发生或死亡，安慰剂组和联合活性药物组之间的 HR 为 1.150（95% 置信区间：0.843-1.570，单边；P = 0.811），该研究于 2007 年 3 月终止。 结论：在这项双盲、随机、安慰剂对照研究。 （肝病学 2011；54：532-540）
Hepatocellular carcinoma (HCC) is characterized by frequent recurrence, even after curative treatment. Vitamin K2, which has been reported to reduce HCC development, may be effective in preventing HCC recurrence. Patients who underwent curative ablation or resection of HCC were randomly assigned to receive placebo, 45 mg/day, or 90 mg/day vitamin K2 in double-blind fashion. HCC recurrence was surveyed every 12 weeks with dynamic computed tomography/magnetic resonance imaging, with HCC-specific tumor markers monitored every 4 weeks. The primary aim was to confirm the superiority of active drug to placebo concerning disease-free survival (DFS), and the secondary aim was to evaluate dose-response relationship. Disease occurrence and death from any cause were treated as events. Hazard ratios (HRs) for disease occurrence and death were calculated using a Cox proportional hazards model. Enrollment was commenced in March 2004. DFS was assessed in 548 patients, including 181 in the placebo group, 182 in the 45-mg/day group, and 185 in the 90-mg/day group. Disease occurrence or death was diagnosed in 58, 52, and 76 patients in the respective groups. The second interim analysis indicated that vitamin K2 did not prevent disease occurrence or death, with an HR of 1.150 (95% confidence interval: 0.843-1.570, one-sided; P = 0.811) between the placebo and combined active-drug groups, and the study was discontinued in March 2007. Conclusion: Efficacy of vitamin K2 in suppressing HCC recurrence was not confirmed in this double-blind, randomized, placebo-controlled study. (HEPATOLOGY 2011;54:532-540)