Hepatic radiofrequency ablation causes an increase of circulating histones in patients with hepatocellular carcinoma
Hepatic radiofrequency ablation causes an increase of circulating histones in patients with hepatocellular carcinoma
复制标题
肝脏射频消融导致肝细胞癌患者循环组蛋白增加
DOI：
10.3109/00365513.2015.1050689
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发表时间：
2015-01-01
影响因子：
2.1
通讯作者：
Wen, Tao
中科院分区：
文献类型：
--
作者：
Gu, Tao;Ge, Yang;Wen, Tao
摘要背景：射频消融(RFA)治疗肝细胞癌已被越来越多的人接受。然而，RFA与明显的全身性炎症反应有关，但对其潜在机制知之甚少。循环组蛋白最近被确定为关键的炎症介质。因此，我们调查了循环组蛋白是否参与了RFA相关的炎症。方法：对42例接受RFA治疗的肝癌患者分别于术前、术后(24 h内)、术后4周(术后4周)采集血样。检测血浆组蛋白、髓过氧化物酶、炎性细胞因子(IL-1、β、IL-6、IL-10、肿瘤坏死因子-α)、肝损伤指标(ALT、AST、肌酐)。结果：与射频消融前(0.837μg/ml)相比，射频消融后24 h内循环组蛋白水平显著升高(4.576μg/ml，p<0.0001)，术后4周随访组蛋白降至射频消融前水平。同时，MPO、IL-6和IL-10在RFA后24小时内显著升高，提示炎症反应的发生。值得注意的是，组蛋白水平分别与MPO(r=0.5678)、IL-6(r=0.4851)和IL-10(r=0.3574)有良好的相关性。此外，患者在RFA后24小时内出现明显的肝功能损害，表现为ALT和AST水平的升高。未观察到肌酐水平的变化。结论：这些数据表明，经RFA治疗的肝癌患者循环中的组蛋白过度释放，这可能通过刺激中性粒细胞激活和促进细胞因子的产生而导致全身炎症。循环组蛋白可作为一种新的标记物来指示与RFA相关的炎症程度。
Abstract Background: Radiofrequency ablation (RFA) has been increasingly accepted for the treatment of hepatocellular carcinoma (HCC). However, RFA has been associated with an obvious systemic inflammatory response, but little is known about the underlying mechanisms. Circulating histones are recently identified as pivotal inflammatory mediators. Hence, we investigated whether circulating histones are involved in RFA-related inflammation. Methods: Serial blood samples were collected from 42 HCC patients undergoing RFA at 3 time points: pre-RFA, post-RFA (within 24 h), and in 4-week follow up after RFA. Plasma histones, myeloperoxidase (MPO), inflammatory cytokines (IL-1β, IL-6, IL-10, TNF-α), liver damage parameters (ALT, AST), and creatinine were measured. Results: Compared to pre-RFA (0.837 μg/ml), there was a significant increase in the levels of circulating histones within 24 h post-RFA (4.576 μg/ml, p < 0.0001); histones decreased to pre-RFA levels in 4-week follow up after RFA. Meanwhile, MPO, IL-6, and IL-10 were elevated remarkably within 24 h post-RFA, indicative of an occurrence of the inflammatory response. Notably, histone levels correlated well with MPO (r = 0.5678), IL-6 (r = 0.4851), and IL-10 (r = 0.3574), respectively. In addition, there was a significant damage of liver function in patients within 24 h post-RFA, evidenced by the increased levels of ALT and AST. No changes in creatinine levels were observed. Conclusions: These data demonstrate that circulating histones are excessively released in HCC patients treated with RFA, which may lead to systemic inflammation by stimulating neutrophil activation and promoting cytokine production. Circulating histones may act as a novel marker to indicate the extent of inflammation related to RFA.