Department of Clinical Chemistry, Karolinska University Hospital, Stockholm, Sweden.
Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Stockholm, Sweden.
Sci Rep. 2021 Sep 9;11(1):18025. doi: 10.1038/s41598-021-97233-3.
Neutrophil extracellular traps (NETs) are web-like structures consisting of DNA, histones and granule proteins, released from neutrophils in thrombus formation, inflammation, and cancer. We asked if plasma levels of the NET markers myeloperoxidase (MPO)-DNA and citrullinated histone H3 (H3Cit)-DNA, are elevated in liver cirrhosis and hepatocellular carcinoma (HCC) and if the levels correlate with clinical parameters. MPO-DNA, H3Cit-DNA, and thrombin-antithrombin (TAT) complex, as a marker of coagulation activity, were measured using ELISA in plasma from 82 patients with HCC, 95 patients with cirrhosis and 50 healthy controls. Correlations were made to clinical parameters and laboratory data and patients were followed for a median of 22.5 months regarding thrombosis development. H3Cit-DNA was significantly (p < 0.01) elevated in plasma from cirrhosis (66.4 ng/mL) and HCC (63.8 ng/mL) patients compared to healthy controls (31.8 ng/mL). TAT levels showed similar pattern (3.1, 3.7, and 0.0 µg/mL respectively, p < 0.01). MPO-DNA was significantly (p < 0.01) elevated in cirrhosis patients (0.53 O.D.) as compared to controls (0.33 O.D.). Levels of MPO-DNA and H3Cit-DNA correlated positively with Child-Pugh and MELD score. TAT was increased in all Child-Pugh and MELD groups. In multivariable logistic regression, Child B and C liver cirrhosis were independent predictors of elevated H3Cit-DNA in plasma. Levels of MPO-DNA and H3Cit-DNA were similar in patients with or without history of thrombosis, or thrombus formation during follow-up. In conclusion, plasma markers of NET formation are elevated in liver cirrhosis and correlate to the degree of liver dysfunction in patients with liver cirrhosis and/or HCC. The presence of HCC did not further increase the plasma levels of NET markers as compared to patients with cirrhosis only.
中性粒细胞胞外诱捕网（NETs）是由中性粒细胞在血栓形成、炎症和癌症中释放的由 DNA、组蛋白和颗粒蛋白组成的网状结构。我们想知道，在肝硬化和肝细胞癌（HCC）中，血浆中 NET 标志物髓过氧化物酶（MPO）-DNA 和瓜氨酸化组蛋白 H3（H3Cit）-DNA 的水平是否升高，以及这些水平是否与临床参数相关。使用 ELISA 法测量了 82 例 HCC 患者、95 例肝硬化患者和 50 例健康对照者血浆中的 MPO-DNA、H3Cit-DNA 和凝血酶-抗凝血酶（TAT）复合物（作为凝血活性的标志物）。对这些参数与临床参数和实验室数据的相关性进行了分析，并对患者进行了中位时间为 22.5 个月的随访，以观察血栓形成的发生情况。与健康对照组（31.8ng/mL）相比，肝硬化（66.4ng/mL）和 HCC（63.8ng/mL）患者的血浆 H3Cit-DNA 水平显著升高（p<0.01）。TAT 水平也呈现相似的模式（分别为 3.1、3.7 和 0.0μg/mL，p<0.01）。与对照组（0.33 O.D.）相比，肝硬化患者的 MPO-DNA 水平显著升高（0.53 O.D.）（p<0.01）。MPO-DNA 和 H3Cit-DNA 水平与 Child-Pugh 和 MELD 评分呈正相关。所有 Child-Pugh 和 MELD 组的 TAT 均升高。多变量逻辑回归分析显示，Child B 和 C 级肝硬化是血浆中 H3Cit-DNA 升高的独立预测因子。在有或无血栓形成史或随访期间有血栓形成史的患者中，MPO-DNA 和 H3Cit-DNA 水平相似。结论：在肝硬化患者中，NET 形成的血浆标志物升高，并与肝硬化患者和/或 HCC 患者肝功能障碍的程度相关。与仅患有肝硬化的患者相比，HCC 的存在并未进一步增加 NET 标志物的血浆水平。
