Jonel Trebicka, Ferran Aguilar, Alberto Queiroz Farias, Juan-José Lozano, Cristina Sánchez-Garrido, Eva Usón-Raposo, Carlos de la Peña-Ramirez, Julia Sidorova, Anna Curto-Vilalta, Patricia Sierra-Casas, Patricia Momoyo Zitelli, Maria Papp, Gustavo Pereira, Paolo Caraceni, Luciana L Goncalves, Carlo Alessandria, Aldo Torre, Wim Laleman, Adrián Gadano, Salvatore Piano, Angelo Z Mattos, Wenyi Gu, Maximilian Joseph Brol, Robert Schierwagen, Frank Erhard Uschner, Julia Fischer, Liliana S C Mendes, Victor Vargas, Mario R Alvares-da-Silva, Raj Mookerjee, Paolo L Bittencourt, Carlos Benitez, Agustín Albillos, Cláudia Couto, Manuel Mendizabal, Rafael Bañares, Claudio L Toledo, Daniel F Mazo, Martin Janicko, Mauricio Castillo-Barradas, Pedro Martin Padilla Machaca, Pietro Gatti, Adelina Zarela-Lozano Miranda, René Malé-Velázquez, Alexander Zipprich, André Castro-Lyra, Thierry Gustot, William Bernal, Alexander L Gerbes, Rajiv Jalan, Javier Fernández, Paolo Angeli, Flair Jose Carrilho, Joan Claria, Richard Moreau, Vicente Arroyo
{"title":"Gene score to quantify systemic inflammation in patients with acutely decompensated cirrhosis","authors":"Jonel Trebicka, Ferran Aguilar, Alberto Queiroz Farias, Juan-José Lozano, Cristina Sánchez-Garrido, Eva Usón-Raposo, Carlos de la Peña-Ramirez, Julia Sidorova, Anna Curto-Vilalta, Patricia Sierra-Casas, Patricia Momoyo Zitelli, Maria Papp, Gustavo Pereira, Paolo Caraceni, Luciana L Goncalves, Carlo Alessandria, Aldo Torre, Wim Laleman, Adrián Gadano, Salvatore Piano, Angelo Z Mattos, Wenyi Gu, Maximilian Joseph Brol, Robert Schierwagen, Frank Erhard Uschner, Julia Fischer, Liliana S C Mendes, Victor Vargas, Mario R Alvares-da-Silva, Raj Mookerjee, Paolo L Bittencourt, Carlos Benitez, Agustín Albillos, Cláudia Couto, Manuel Mendizabal, Rafael Bañares, Claudio L Toledo, Daniel F Mazo, Martin Janicko, Mauricio Castillo-Barradas, Pedro Martin Padilla Machaca, Pietro Gatti, Adelina Zarela-Lozano Miranda, René Malé-Velázquez, Alexander Zipprich, André Castro-Lyra, Thierry Gustot, William Bernal, Alexander L Gerbes, Rajiv Jalan, Javier Fernández, Paolo Angeli, Flair Jose Carrilho, Joan Claria, Richard Moreau, Vicente Arroyo","doi":"10.1136/gutjnl-2024-333876","DOIUrl":null,"url":null,"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. Data are available on reasonable request.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"10 1","pages":""},"PeriodicalIF":23.0000,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Gut","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1136/gutjnl-2024-333876","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
引用次数: 0
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. Data are available on reasonable request.
期刊介绍:
Gut is a renowned international journal specializing in gastroenterology and hepatology, known for its high-quality clinical research covering the alimentary tract, liver, biliary tree, and pancreas. It offers authoritative and current coverage across all aspects of gastroenterology and hepatology, featuring articles on emerging disease mechanisms and innovative diagnostic and therapeutic approaches authored by leading experts.
As the flagship journal of BMJ's gastroenterology portfolio, Gut is accompanied by two companion journals: Frontline Gastroenterology, focusing on education and practice-oriented papers, and BMJ Open Gastroenterology for open access original research.