Journal Article

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

Jimenez, Cesar, Coenraad, Minneke, Praktiknjo, Michael, Baldassarre, Maurizio, Goncalves, Luciana L, Mendes, Liliana S C, Putignano, Antonella, Mareso, Sara, Pagés, Josefina, Uschner, Frank Erhard, Colombato, Luis, Altorjay, Istvan, Maschmeier, Miriam, Ende, Natalie den, Bernardi, Mauro, Ortiz, Leyla Nazal, Solé, Cristina, Estanes-Hernández, Alma, Soriano, Germán, Sidorova, Julia, Ryder, Stephen, de la Peña-Ramirez, Carlos, Salomón, Marcos Girala, Bruns, Tony, Mantovani, Augusto, Samuel, Didier, Vargas, Victor, Bittencourt, Paolo L, Ciraci, Emanuela, Valdivia, Raúl Castro, Malé-Velázquez, René, Vanderschueren, Emma, Zaccherini, Giacomo, Francque, Sven, Rupprechter, Harald, Piano, Salvatore, Simón-Talero, Macarena, Manriquez, Jesús Ruiz, Fainboim, Hugo, Vitalis, Zsuzsanna, Terra, Carlos, Saracco, Giorgio Maria, Berg, Thomas, Vlierberghe, Hans Van, Martinez-Garmendia, Agustina, Angeli, Paolo, Sierra-Casas, Patricia, Sánchez-Garrido, Cristina, Curto-Vilalta, Anna, Momoyo Zitelli, Patricia, Zeuzem, Stefan, Patel, Vish, Claria, Joan, Gu, Wenyi, Alvares-da-Silva, Mario R, Castro-Lyra, André, Jarcuska,

2025

Overview

Background and aimsQuantifying 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.MethodsStandard 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.ResultsThe 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.ConclusionsIn patients with ADC, the CLIF-SIG score is an accurate estimator of SI, clinical course severity and prognosis.

• Publisher: BMJ Publishing Group Ltd and British Society of Gastroenterology,BMJ Publishing Group LTD
• Subject: Acute-On-Chronic Liver Failure - blood / Acute-On-Chronic Liver Failure - etiology / Acute-On-Chronic Liver Failure - genetics / Aged / Biomarkers / Biomarkers - blood / C-reactive protein / C-Reactive Protein - analysis / CIRRHOSIS / Cytokines / Cytokines - blood / Female / Gene expression / Genes / GENETICS / Hepatology / Hospitalization / Hospitals / Humans / IMMUNOLOGY IN HEPATOLOGY / INFLAMMATION / Inflammation - blood / Inflammation - genetics / Leukocyte Count / Liver / Liver cirrhosis / Liver Cirrhosis - blood / Liver Cirrhosis - complications / Liver Cirrhosis - genetics / Liver diseases / LIVER FAILURE / Lymphocytes / Male / Middle Aged / Mortality / Neutrophils / Patients / Phenotypes / Severity of Illness Index