Gene score to quantify systemic inflammation in patients with acutely decompensated cirrhosis

作者：Jonel Trebicka, Ferrán Aguilar, Alberto Queiróz Farias, Juan José Lozano, Cristina Sánchez-Garrido, Eva Usón-Raposo, Carlos de la Peña-Ramirez, Julia Sidorova, Anna Curto, Patricia Sierra-Casas, Patrícia Momoyo Zitelli, Mária Papp, Gustavo Pereira, Paolo Caraceni, Luciana L Goncalves, Carlo Alessandria, Aldo Torre, Wim Laleman, Adrián Gadano, Salvatore Piano, Ângelo Zambam de Mattos, Wen Gu, Maximilian Joseph Brol, Robert Schierwagen, Frank Erhard Uschner, Julia Fischer, Liliana Sampaio Costa Mendes, Víctor Manuel Vargas, Mário Reis Álvares‐da‐Silva, Rajeshwar P. Mookerjee, Paulo Lisboa Bittencourt, Carlos Benítez, Agustı́n Albillos, Cláudia Alves Couto, Manuel Mendizábal, Rafael Bañares, Claudio Toledo, Daniel Ferraz de Campos Mazo, Martin Janíčko, M. Castillo-Barradas, Martín Padilla, Pietro Gatti, Alina Miranda, R. Malé-Velázquez, Alexander Zipprich, André Castro-Lyra, Thierry Gustot, William Bernal, Alexander L. Gerbes, Rajiv Jalan, Javier Fernández, Paolo Angeli, Flair José Carrilho, Joan Clària, Richard Moreau, Vicente Arroyo · 发表于：Gut · 年份：2025 · DOI：10.1136/gutjnl-2024-333876 · 被引用次数：14 · 研究领域：Liver Disease and Transplantation、Immune Response and Inflammation、Sepsis Diagnosis and Treatment

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...