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. 2025 Jul 7;74(8):1293-1307.
doi: 10.1136/gutjnl-2024-333876.

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

Jonel Trebicka #  1   2 , Ferran Aguilar #  2   3 , Alberto Queiroz Farias #  4 , Juan-José Lozano #  5 , Cristina Sánchez-Garrido  2 , Eva Usón-Raposo  2 , Carlos de la Peña-Ramirez  2 , Julia Sidorova  5 , Anna Curto-Vilalta  2 , Patricia Sierra-Casas  2 , Patricia Momoyo Zitelli  4 , Maria Papp  6 , Gustavo Pereira  7 , Paolo Caraceni  8   9 , Luciana L Goncalves  10 , Carlo Alessandria  11 , Aldo Torre  12 , Wim Laleman  13   14 , Adrián Gadano  15 , Salvatore Piano  16 , Angelo Z Mattos  17 , Wenyi Gu  13   18 , Maximilian Joseph Brol  13 , Robert Schierwagen  13 , Frank Erhard Uschner  13   18 , Julia Fischer  13 , Liliana S C Mendes  19 , Victor Vargas  20 , Mario R Alvares-da-Silva  21 , Raj Mookerjee  22 , Paolo L Bittencourt  23 , Carlos Benitez  24 , Agustín Albillos  25 , Cláudia Couto  26 , Manuel Mendizabal  27 , Rafael Bañares  28 , Claudio L Toledo  29 , Daniel F Mazo  30 , Martin Janicko  31 , Mauricio Castillo-Barradas  32 , Pedro Martin Padilla Machaca  33 , Pietro Gatti  34 , Adelina Zarela-Lozano Miranda  35 , René Malé-Velázquez  36 , Alexander Zipprich  37 , André Castro-Lyra  38   39 , Thierry Gustot  40 , William Bernal  41 , Alexander L Gerbes  42 , Rajiv Jalan  22 , Javier Fernández  2 , Paolo Angeli  2   43 , Flair Jose Carrilho  44 , Joan Claria  2   45 , Richard Moreau  2   46   47 , Vicente Arroyo  2 ; PREDICT study and ACLARA study
Collaborators, Affiliations
Free article

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

Jonel Trebicka et al. Gut. .
Free article

Erratum in

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.

Keywords: CIRRHOSIS; GENETICS; IMMUNOLOGY IN HEPATOLOGY; INFLAMMATION; LIVER FAILURE.

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Conflict of interest statement

Competing interests: JT has received speaking and/or consulting fees from Versantis, Gore, Boehringer-Ingelheim, Falk, Grifols, Genfit and CSL Behring; PA received lecture fees from BioMarin, Grifols and has served on the advisory board for Biovie and BioMarin; WB received consulting fees from Versantis and Flagship Pioneering; PC received grant support from Grifols SA and Octapharma SA, lecture fees from Grifols SA, Octapharma SA, Takeda SA and CSL Behring SA and has served on the data safety advisory board for Grifols SA, Takeda SA and CSL Behring SA; MM received speaking fees/consulting: Biosidus, Gador, Gilead Sciences, Intercept, Knight, Roche; JFer received lecture fees from Grifols SA; TG received a research grant from Gilead and has served on the advisory board for GoLiver Therapeutics and Cellaïon; RJ had research collaborations with Yaqrit and Takeda, is the inventor of OPA, which has been patented by UCL and licensed to Mallinckrodt Pharma and is the founder of Yaqrit Limited, a spin-off company from University College London and Thoeris; RMor received consulting fees from Genfit and CSL Behring; SP received consulting fees from the Plasma Protein Therapeutics Association, Boehringer Ingelheim and lecture fees from Grifols, Ferring and MEDSCAPE; WL has received consultancy fees from CSL Behring, MRM Health, Cook Medical and Boston-Scientific; AZ received speaking and consulting fees from Gore, Falk, CSL Behring and Grifols. The remaining authors disclosed no conflicts.

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