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中性粒细胞胞外陷阱内稳态失衡与失代偿期肝硬化患者门静脉血栓形成相关。

The Imbalance of Homeostasis in Neutrophil Extracellular Traps is Associated with Portal Vein Thrombosis in Patients with Decompensated Cirrhosis.

作者信息

Han Ming, Liu Yujia, Cao Ying, Zhang Yue, Yan Yonghong, Deng Shuwei, Yuan Xiaoxue, Xing Huichun, Huang Yuan, Zhu Liuluan

机构信息

Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China.

Beijing Institute of Infectious Diseases, Beijing, China.

出版信息

J Clin Transl Hepatol. 2024 Dec 28;12(12):1009-1019. doi: 10.14218/JCTH.2024.00165. Epub 2024 Nov 4.

Abstract

BACKGROUND AND AIMS

Portal vein thrombosis (PVT) is a challenging complication in liver cirrhosis, with no currently available sensitive diagnostic markers. This study aimed to investigate the potential of neutrophil extracellular traps (NETs) and Deoxyribonuclease (DNase) as diagnostic indicators for PVT in chronic hepatitis B (CHB)-related decompensated cirrhosis.

METHODS

We analyzed 145 CHB-related decompensated cirrhosis patients from the Ditan study and 33 from the Changgung validation study, categorizing them based on PVT occurrence. Plasma samples were assessed for NET markers, including cell-free DNA (cfDNA) and histone-DNA complexes, along with DNase activity.

RESULTS

PVT patients exhibited elevated levels of cfDNA and histone-DNA complexes, and reduced DNase activity. This pattern persisted regardless of hepatocellular carcinoma (HCC) status. Histone-DNA levels, DNase activity, and hemoglobin were identified as independent risk factors for PVT. Receiver operating characteristic curve analysis revealed that high histone-DNA levels may serve as a potential diagnostic marker for PVT, with an area under the curve of 0.8628 in the Ditan study and 0.7521 in the Changgung study. When combined with cfDNA and DNase activity, the area under the curve improved to 0.8774 in the Ditan study and 0.7975 in the Changgung study.

CONCLUSIONS

Imbalances in NET homeostasis are associated with PVT in CHB-related decompensated cirrhosis, including cases involving HCC. Histone-DNA complexes, a significant risk factor for PVT, show potential as a diagnostic marker for PVT in decompensated cirrhosis, particularly in HBV-related HCC.

摘要

背景与目的

门静脉血栓形成(PVT)是肝硬化中具有挑战性的并发症,目前尚无灵敏的诊断标志物。本研究旨在探讨中性粒细胞胞外陷阱(NETs)和脱氧核糖核酸酶(DNase)作为慢性乙型肝炎(CHB)相关失代偿期肝硬化患者PVT诊断指标的潜力。

方法

我们分析了来自地坛研究的145例CHB相关失代偿期肝硬化患者和来自长庚验证研究的33例患者,根据PVT的发生情况进行分类。评估血浆样本中的NET标志物,包括游离DNA(cfDNA)和组蛋白-DNA复合物,以及DNase活性。

结果

PVT患者的cfDNA和组蛋白-DNA复合物水平升高,DNase活性降低。无论肝细胞癌(HCC)状态如何,这种模式均持续存在。组蛋白-DNA水平、DNase活性和血红蛋白被确定为PVT的独立危险因素。受试者工作特征曲线分析显示,高组蛋白-DNA水平可能作为PVT的潜在诊断标志物,在地坛研究中的曲线下面积为0.8628,在长庚研究中为0.7521。当与cfDNA和DNase活性相结合时,地坛研究中的曲线下面积提高到0.8774,长庚研究中为0.7975。

结论

NET内稳态失衡与CHB相关失代偿期肝硬化患者的PVT有关,包括合并HCC的病例。组蛋白-DNA复合物是PVT的重要危险因素,在失代偿期肝硬化,尤其是HBV相关HCC中显示出作为PVT诊断标志物的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9206/11622206/95273fc891d0/JCTH-12-1009-g001.jpg

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