Gene score to quantify systemic inflammation in patients with acutely decompensated cirrhosis
Author(s)
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
Date Issued
26 de febrero de 2025
Type
Article
Volume
74
Issue
8
Start Page
1293
End Page
1307
Abstract
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.
Subjects