用于量化急性失代偿期肝硬化患者全身炎症的基因评分。
Gene score to quantify systemic inflammation in patients with acutely decompensated cirrhosis.
作者信息
Trebicka Jonel, Aguilar Ferran, Queiroz Farias Alberto, Lozano Juan-José, Sánchez-Garrido Cristina, Usón-Raposo Eva, de la Peña-Ramirez Carlos, Sidorova Julia, Curto-Vilalta Anna, Sierra-Casas Patricia, Momoyo Zitelli Patricia, Papp Maria, Pereira Gustavo, Caraceni Paolo, Goncalves Luciana L, Alessandria Carlo, Torre Aldo, Laleman Wim, Gadano Adrián, Piano Salvatore, Mattos Angelo Z, Gu Wenyi, Brol Maximilian Joseph, Schierwagen Robert, Uschner Frank Erhard, Fischer Julia, Mendes Liliana S C, Vargas Victor, Alvares-da-Silva Mario R, Mookerjee Raj, Bittencourt Paolo L, Benitez Carlos, Albillos Agustín, Couto Cláudia, Mendizabal Manuel, Bañares Rafael, Toledo Claudio L, Mazo Daniel F, Janicko Martin, Castillo-Barradas Mauricio, Padilla Machaca Pedro Martin, Gatti Pietro, Miranda Adelina Zarela-Lozano, Malé-Velázquez René, Zipprich Alexander, Castro-Lyra André, Gustot Thierry, Bernal William, Gerbes Alexander L, Jalan Rajiv, Fernández Javier, Angeli Paolo, Carrilho Flair Jose, Claria Joan, Moreau Richard, Arroyo Vicente
机构信息
Department of Internal Medicine B, University of Münster, Munster, Germany
European Foundation for the Study of Chronic Liver Failure (EF CLIF), Barcelona, Spain.
出版信息
Gut. 2025 Jul 7;74(8):1293-1307. doi: 10.1136/gutjnl-2024-333876.
BACKGROUND AND AIMS
Quantifying systemic inflammation (SI) in acutely decompensated cirrhosis (ADC) is of major importance because SI is a driver of the most severe forms of ADC, including acute-on-chronic liver failure (ACLF). Blood biomarkers of SI already evaluated in ADC failed to appropriately assess SI in ADC. We aimed to investigate whether gene expression related to circulating immune cells could quantify SI in ADC.
METHODS
Standard biomarkers (white cell count, C reactive protein, cytokines) and genome-wide RNA expression (RNA-sequencing) were obtained in blood from 700 patients with ADC at the time of their hospital admission. A composite score based on standard biomarkers of SI (Chronic Liver Failure-Standard Biomarkers Composite (CLIF-SBC) score) and a gene score (CLIF-Systemic Inflammation Gene (SIG) score) composed of the 28 top differentially expressed immune cell-related genes in the comparison between high-severity and low-severity clinical phenotypes were computed. Among the 700 patients, the CLIF-SIG score was repeated once during follow-up in 375 patients, and 3 times or more in 46 patients.
RESULTS
The CLIF-SIG score was more accurate in reflecting clinical severity induced by SI than the CLIF-SBC score (area under the curve 0.803 vs 0.658). A CLIF-SIG score of 0.386 (Youden Index) was the best cut-off level discriminating patients with poor outcomes from the others, in all clinical scenarios. Sequential measurement of the CLIF-SIG score showed that 78% of patients were admitted at the peak or descending part of the SI-wave. ACLF developed during hospitalisation in 80% of patients with a CLIF-SIG score >0.386 on admission.
CONCLUSIONS
In patients with ADC, the CLIF-SIG score is an accurate estimator of SI, clinical course severity and prognosis.
背景与目的
量化急性失代偿期肝硬化（ADC）中的全身炎症（SI）至关重要，因为SI是包括慢加急性肝衰竭（ACLF）在内的最严重形式的ADC的驱动因素。已在ADC中评估的SI血液生物标志物未能适当评估ADC中的SI。我们旨在研究与循环免疫细胞相关的基因表达是否可以量化ADC中的SI。
方法
在700例ADC患者入院时采集血液样本，检测标准生物标志物（白细胞计数、C反应蛋白、细胞因子）和全基因组RNA表达（RNA测序）。计算基于SI标准生物标志物的综合评分（慢性肝衰竭-标准生物标志物综合（CLIF-SBC）评分）和由高严重度与低严重度临床表型比较中28个差异表达最高的免疫细胞相关基因组成的基因评分（CLIF-全身炎症基因（SIG）评分）。在700例患者中，375例患者在随访期间重复检测一次CLIF-SIG评分，46例患者重复检测3次或更多次。
结果
CLIF-SIG评分在反映SI引起的临床严重程度方面比CLIF-SBC评分更准确（曲线下面积分别为0.803和0.658）。在所有临床情况下，CLIF-SIG评分为0.386（约登指数）是区分预后不良患者与其他患者的最佳临界值。CLIF-SIG评分的连续测量显示，78%的患者在SI波的峰值或下降部分入院。入院时CLIF-SIG评分>0.386的患者中，80%在住院期间发生ACLF。
结论
在ADC患者中，CLIF-SIG评分是SI、临床病程严重程度和预后的准确评估指标。
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