Portal hemodynamic effects of sorafenib in patients with advanced hepatocellular carcinoma: a prospective cohort study
Portal hemodynamic effects of sorafenib in patients with advanced hepatocellular carcinoma: a prospective cohort study
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DOI：
10.1007/s00535-012-0563-6
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发表时间：
2012-09-01
影响因子：
6.3
通讯作者：
Koizumi, Wasaburo
中科院分区：
文献类型：
--
作者：
Hidaka, Hisashi;Nakazawa, Takahide;Koizumi, Wasaburo
索拉非尼目前在临床上用作口服多激酶抑制剂，可阻止晚期肝细胞癌 (HCC) 的肿瘤生长和细胞增殖。一项转化研究表明，索拉非尼对患有门脉高压的肝硬化动物的门侧支循环具有有益作用。本研究采用前瞻性研究，利用双功多普勒超声检查 (DDU) 评估索拉非尼对晚期 HCC 患者门脉血流动力学的影响。25 名 Child-Pugh A 级晚期 HCC 患者接受索拉非尼治疗，剂量为 400 mg，每日两次。主要结果是在索拉非尼给药 2 周之前和之后使用 DDU 观察到门静脉面积 (PVA；cm(2)) 的变化。次要结局包括 DDU 上显示的实验室数据和其他流量数据的变化。给药 2 周后，PVA 显着降低（0.78 +/- A 0.23 对比 0.64 +/- A 0.25，P = 0.023），而门静脉流速（PVV；cm/s）没有显着变化（0.22 +/- A 0.06 对比 0.24 +/- A 0.07， P = 0.17）。因此，反映门静脉系统病理生理血流动力学的充血指数（PVA/PVV）显着降低（3.9+/-A 1.7 vs. 3.0+/-A 1.4，P=0.042）。我们证明了索拉非尼对晚期HCC患者门静脉血流动力学的影响。考虑到这是一项短期研究，由于索拉非尼可能是门静脉高压症的潜在有益治疗药物，因此有必要在未来的研究中验证其对门静脉高压症的临床益处。
Sorafenib is currently in clinical use as an oral multikinase inhibitor that blocks tumor growth and cell proliferation in advanced hepatocellular carcinoma (HCC). It has been demonstrated in a translating study that sorafenib had a beneficial effect on portocollateral circulation in cirrhotic animals with portal hypertension. This study was prospectively performed to evaluate the portal hemodynamic effect of sorafenib in patients with advanced HCC using duplex Doppler ultrasonography (DDU).Twenty-five Child-Pugh class-A patients with advanced HCC had received sorafenib at a dose of 400 mg twice daily. Primary outcomes were changes in portal venous area (PVA; cm(2)) as seen by using DDU before and after a 2-week administration of sorafenib. Secondary outcomes included the changes of laboratory data and other flow data revealed on DDU.PVA was significantly decreased after a 2-week administration (0.78 +/- A 0.23 vs. 0.64 +/- A 0.25, P = 0.023), while the portal venous flow velocity (PVV; cm/s) was not significantly changed (0.22 +/- A 0.06 vs. 0.24 +/- A 0.07, P = 0.17). Therefore, the congestion index (PVA/PVV), which reflects the pathophysiological hemodynamics of portal venous system, was significantly decreased (3.9 +/- A 1.7 vs. 3.0 +/- A 1.4, P = 0.042).We demonstrated the portal hemodynamic effect of sorafenib in patients with advanced HCC. Considering that this was a short-term study, because sorafenib could be a potential beneficial therapeutic agent for portal hypertension, it will be necessary to verify its clinical benefits for portal hypertension in future studies.