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系统性炎症作为肝硬化门静脉血栓形成的危险因素:一项前瞻性纵向研究。

Systemic inflammation as a risk factor for portal vein thrombosis in cirrhosis: a prospective longitudinal study.

机构信息

Transplantation Department, Unidade de Transplante Hepato-Pancreática, Centro Hospitalar Universitário do Porto, Porto, Portugal.

EPI Unit - Instituto de Saúde Pública da Universidade do Porto.

出版信息

Eur J Gastroenterol Hepatol. 2021 Dec 1;33(1S Suppl 1):e108-e113. doi: 10.1097/MEG.0000000000001982.

Abstract

BACKGROUND AND AIMS

Various risk factors for portal vein thrombosis (PVT) development in patients with cirrhosis have been identified, but the role of systemic inflammatory reaction is unknown. The study aims to assess the association between markers of systemic inflammation and PVT in cirrhosis.

METHODS

Between January 2014 and October 2015, 107 outpatients with cirrhosis and no PVT were recruited, and followed till February 2017. White blood cell count, serum concentrations of high-sensitive C-reactive protein, ferritin, tumor necrosis factor-alpha and interleukin-6 (IL-6) were evaluated at baseline and every 3 or 6 months till PVT diagnosis or end of follow-up.

RESULTS

Median age, model for end-stage liver disease (MELD) score and follow-up period of the studied population was 55 years (IQR 46-62 years), 9.6 points (IQR 7.5-12 points) and 19 months (12-24 months), respectively. PVT developed in 10.3% of the patients. Lymphocyte count below 1.2 ´ 109/L [hazard ratio, 6.04; 95% confidence interval (CI), 1.29-28.2; P = 0.022], IL-6 above 5.5 pg/mL (hazard ratio, 5.64; 95% CI, 1.21-26.33; P  = 0.028) and neutrophil-to-lymphocyte ratio (hazard ratio, 1.46; 95% CI, 1.04-2.04; P = 0.028) were associated with a higher risk of PVT development. IL-6 and lymphopenia remained associated with subsequent PVT development after adjustment for nonselective beta-blockers, spleen size, portosystemic collaterals, oesophageal varices (grade ≥2) and ascites, but also with alcohol as the cause for cirrhosis and MELD ≥13.

CONCLUSION

In patients with cirrhosis, markers of systemic inflammation IL-6 and lymphopenia are predictive of PVT independently of markers of portal hypertension. These results draw our attention on a factor so far overlooked in the pathogenesis of PVT.

摘要

背景与目的

已确定了多种导致肝硬化患者门静脉血栓形成(PVT)的风险因素,但系统炎症反应的作用尚不清楚。本研究旨在评估肝硬化患者全身炎症标志物与 PVT 之间的关系。

方法

2014 年 1 月至 2015 年 10 月,招募了 107 名无 PVT 的肝硬化门诊患者,并随访至 2017 年 2 月。在基线时以及每 3 或 6 个月评估白细胞计数、超敏 C 反应蛋白、铁蛋白、肿瘤坏死因子-α和白细胞介素-6(IL-6)的血清浓度,直至 PVT 诊断或随访结束。

结果

研究人群的中位年龄、终末期肝病模型(MELD)评分和随访时间分别为 55 岁(四分位距 46-62 岁)、9.6 分(四分位距 7.5-12 分)和 19 个月(12-24 个月)。10.3%的患者发生了 PVT。淋巴细胞计数低于 1.2´109/L[风险比(HR),6.04;95%置信区间(CI),1.29-28.2;P=0.022]、IL-6 高于 5.5pg/mL(HR,5.64;95%CI,1.21-26.33;P=0.028)和中性粒细胞与淋巴细胞比值(HR,1.46;95%CI,1.04-2.04;P=0.028)与 PVT 发生风险较高相关。在校正非选择性β受体阻滞剂、脾脏大小、门体侧支循环、食管静脉曲张(≥2 级)和腹水后,IL-6 和淋巴细胞减少与随后的 PVT 发生仍相关,但也与酒精性肝硬化和 MELD≥13 相关。

结论

在肝硬化患者中,全身炎症标志物 IL-6 和淋巴细胞减少可独立于门静脉高压标志物预测 PVT。这些结果使我们注意到迄今为止在 PVT 发病机制中被忽视的一个因素。

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