Department of Gastroenterology, Internal Medicine, Kitasato University East Hospital, 2-1-1 Asamizodai, Minami-ku, Sagamihara, Kanagawa 252-0380, Japan.
J Gastroenterol. 2012 Sep;47(9):1030-5. doi: 10.1007/s00535-012-0563-6. Epub 2012 Mar 9.
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 ± 0.23 vs. 0.64 ± 0.25, P = 0.023), while the portal venous flow velocity (PVV; cm/s) was not significantly changed (0.22 ± 0.06 vs. 0.24 ± 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 ± 1.7 vs. 3.0 ± 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.
索拉非尼是一种临床应用的口服多激酶抑制剂,可阻断晚期肝细胞癌(HCC)中的肿瘤生长和细胞增殖。一项转化研究表明,索拉非尼可对伴有门脉高压的肝硬化动物的门体侧支循环产生有益影响。本前瞻性研究采用双功能多普勒超声(DDU)评估索拉非尼对晚期 HCC 患者的门脉血流动力学的影响。
25 例 Child-Pugh 分级为 A 的晚期 HCC 患者接受索拉非尼治疗,剂量为 400mg,每日两次。主要终点是使用 DDU 在索拉非尼治疗前和治疗后 2 周时门静脉面积(PVA;cm²)的变化。次要终点包括 DDU 显示的实验室数据和其他血流数据的变化。
治疗 2 周后 PVA 显著下降(0.78 ± 0.23 比 0.64 ± 0.25,P = 0.023),而门静脉血流速度(PVV;cm/s)无显著变化(0.22 ± 0.06 比 0.24 ± 0.07,P = 0.17)。因此,反映门脉系统病理生理学血流动力学的充血指数(PVA/PVV)显著降低(3.9 ± 1.7 比 3.0 ± 1.4,P = 0.042)。
我们证实了索拉非尼对晚期 HCC 患者的门脉血流动力学的影响。由于这是一项短期研究,索拉非尼可能是门脉高压的潜在有益治疗药物,因此需要在未来的研究中验证其对门脉高压的临床益处。