Gene score to quantify systemic inflammation in patients with acutely decompensated cirrhosis
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...
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| author | 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 |
| author_browse | Adrián Gadano Agustı́n Albillos Alberto Queiróz Farias Aldo Torre Alexander L. Gerbes Alexander Zipprich Alina Miranda André Castro-Lyra Anna Curto Carlo Alessandria Carlos Benítez Carlos de la Peña-Ramirez Claudio Toledo Cláudia Alves Couto Cristina Sánchez-Garrido Daniel Ferraz de Campos Mazo Eva Usón-Raposo Ferrán Aguilar Flair José Carrilho Frank Erhard Uschner Gustavo Pereira Javier Fernández Joan Clària Jonel Trebicka Juan José Lozano Julia Fischer Julia Sidorova Liliana Sampaio Costa Mendes Luciana L Goncalves M. Castillo-Barradas Manuel Mendizábal Martin Janíčko Martín Padilla Maximilian Joseph Brol Mária Papp Mário Reis Álvares‐da‐Silva Paolo Angeli Paolo Caraceni Patricia Sierra-Casas Patrícia Momoyo Zitelli Paulo Lisboa Bittencourt Pietro Gatti R. Malé-Velázquez Rafael Bañares Rajeshwar P. Mookerjee Rajiv Jalan Richard Moreau Robert Schierwagen Salvatore Piano Thierry Gustot Vicente Arroyo Víctor Manuel Vargas Wen Gu William Bernal Wim Laleman Ângelo Zambam de Mattos |
| author_facet | 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 |
| author_sort | Jonel Trebicka |
| collection | Producción científica |
| description | 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. |
| format | Article |
| id | oai:cris.upeu.edu.pe:20.500.15037/1355 |
| institution | UPeU |
| language | English |
| publishDate | 2025 |
| publishDateRange | 2025 |
| publishDateSort | 2025 |
| record_format | dspace |
| spelling | oai:cris.upeu.edu.pe:20.500.15037/13552026-10-30T16:15:38ZGene score to quantify systemic inflammation in patients with acutely decompensated cirrhosisJonel TrebickaFerrán AguilarAlberto Queiróz FariasJuan José LozanoCristina Sánchez-GarridoEva Usón-RaposoCarlos de la Peña-RamirezJulia SidorovaAnna CurtoPatricia Sierra-CasasPatrícia Momoyo ZitelliMária PappGustavo PereiraPaolo CaraceniLuciana L GoncalvesCarlo AlessandriaAldo TorreWim LalemanAdrián GadanoSalvatore PianoÂngelo Zambam de MattosWen GuMaximilian Joseph BrolRobert SchierwagenFrank Erhard UschnerJulia FischerLiliana Sampaio Costa MendesVíctor Manuel VargasMário Reis Álvares‐da‐SilvaRajeshwar P. MookerjeePaulo Lisboa BittencourtCarlos BenítezAgustı́n AlbillosCláudia Alves CoutoManuel MendizábalRafael BañaresClaudio ToledoDaniel Ferraz de Campos MazoMartin JaníčkoM. Castillo-BarradasMartín PadillaPietro GattiAlina MirandaR. Malé-VelázquezAlexander ZipprichAndré Castro-LyraThierry GustotWilliam BernalAlexander L. GerbesRajiv JalanJavier FernándezPaolo AngeliFlair José CarrilhoJoan ClàriaRichard MoreauVicente ArroyoMedicineSystemic inflammationCirrhosisWhite blood cellInternal medicineInflammationFramingham Risk ScoreImmune systemGastroenterologyOncologyImmunologyDiseaseMedicineSystemic inflammationCirrhosisWhite blood cellInternal medicineInflammationFramingham Risk ScoreImmune systemGastroenterologyOncologyImmunologyAgedAgedAgedC-Reactive Protein analysisC-Reactive Protein analysisC-Reactive Protein analysisFemaleFemaleFemaleHumansHumansHumansInflammation bloodInflammation bloodInflammation bloodInflammation geneticsInflammation geneticsInflammation geneticsLeukocyte CountLeukocyte CountLeukocyte CountLiver Cirrhosis bloodLiver Cirrhosis bloodLiver Cirrhosis bloodLiver Cirrhosis complicationsLiver Cirrhosis complicationsLiver Cirrhosis complicationsLiver Cirrhosis geneticsLiver Cirrhosis geneticsLiver Cirrhosis geneticsMaleMaleMaleMiddle AgedMiddle AgedMiddle AgedSeverity of Illness IndexSeverity of Illness IndexSeverity of Illness IndexBiomarkers bloodBiomarkers bloodBiomarkers bloodCytokines bloodCytokines bloodCytokines bloodAcute-On-Chronic Liver Failure bloodAcute-On-Chronic Liver Failure bloodAcute-On-Chronic Liver Failure bloodAcute-On-Chronic Liver Failure etiologyAcute-On-Chronic Liver Failure etiologyAcute-On-Chronic Liver Failure etiologyAcute-On-Chronic Liver Failure geneticsAcute-On-Chronic Liver Failure geneticsAcute-On-Chronic Liver Failure geneticsHealth Sciences Medicine Hepatology Liver Disease and TransplantationLife Sciences Immunology and Microbiology Immunology Immune Response and InflammationHealth Sciences Medicine Epidemiology Sepsis Diagnosis and TreatmentBACKGROUND 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.Articlehttps://pubmed.ncbi.nlm.nih.gov/40011033https://gut.bmj.com/content/gutjnl/early/2025/02/26/gutjnl-2024-333876.full.pdfhttps://doi.org/10.1136/gutjnl-2024-33387610.1136/gutjnl-2024-333876https://hdl.handle.net/20.500.15037/1355W4407953731enGut0017-57491468-32882025-02-262026-06-13T09:54:48Z2026-06-13T09:54:48Z |
| spellingShingle | Medicine Systemic inflammation Cirrhosis White blood cell Internal medicine Inflammation Framingham Risk Score Immune system Gastroenterology Oncology Immunology Disease Medicine Systemic inflammation Cirrhosis White blood cell Internal medicine Inflammation Framingham Risk Score Immune system Gastroenterology Oncology Immunology Aged Aged Aged C-Reactive Protein analysis C-Reactive Protein analysis C-Reactive Protein analysis Female Female Female Humans Humans Humans Inflammation blood Inflammation blood Inflammation blood Inflammation genetics Inflammation genetics Inflammation genetics Leukocyte Count Leukocyte Count Leukocyte Count Liver Cirrhosis blood Liver Cirrhosis blood Liver Cirrhosis blood Liver Cirrhosis complications Liver Cirrhosis complications Liver Cirrhosis complications Liver Cirrhosis genetics Liver Cirrhosis genetics Liver Cirrhosis genetics Male Male Male Middle Aged Middle Aged Middle Aged Severity of Illness Index Severity of Illness Index Severity of Illness Index Biomarkers blood Biomarkers blood Biomarkers blood Cytokines blood Cytokines blood Cytokines blood Acute-On-Chronic Liver Failure blood Acute-On-Chronic Liver Failure blood Acute-On-Chronic Liver Failure blood Acute-On-Chronic Liver Failure etiology Acute-On-Chronic Liver Failure etiology Acute-On-Chronic Liver Failure etiology Acute-On-Chronic Liver Failure genetics Acute-On-Chronic Liver Failure genetics Acute-On-Chronic Liver Failure genetics Health Sciences Medicine Hepatology Liver Disease and Transplantation Life Sciences Immunology and Microbiology Immunology Immune Response and Inflammation Health Sciences Medicine Epidemiology Sepsis Diagnosis and Treatment 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 Gene score to quantify systemic inflammation in patients with acutely decompensated cirrhosis |
| title | Gene score to quantify systemic inflammation in patients with acutely decompensated cirrhosis |
| title_full | Gene score to quantify systemic inflammation in patients with acutely decompensated cirrhosis |
| title_fullStr | Gene score to quantify systemic inflammation in patients with acutely decompensated cirrhosis |
| title_full_unstemmed | Gene score to quantify systemic inflammation in patients with acutely decompensated cirrhosis |
| title_short | Gene score to quantify systemic inflammation in patients with acutely decompensated cirrhosis |
| title_sort | gene score to quantify systemic inflammation in patients with acutely decompensated cirrhosis |
| topic | Medicine Systemic inflammation Cirrhosis White blood cell Internal medicine Inflammation Framingham Risk Score Immune system Gastroenterology Oncology Immunology Disease Medicine Systemic inflammation Cirrhosis White blood cell Internal medicine Inflammation Framingham Risk Score Immune system Gastroenterology Oncology Immunology Aged Aged Aged C-Reactive Protein analysis C-Reactive Protein analysis C-Reactive Protein analysis Female Female Female Humans Humans Humans Inflammation blood Inflammation blood Inflammation blood Inflammation genetics Inflammation genetics Inflammation genetics Leukocyte Count Leukocyte Count Leukocyte Count Liver Cirrhosis blood Liver Cirrhosis blood Liver Cirrhosis blood Liver Cirrhosis complications Liver Cirrhosis complications Liver Cirrhosis complications Liver Cirrhosis genetics Liver Cirrhosis genetics Liver Cirrhosis genetics Male Male Male Middle Aged Middle Aged Middle Aged Severity of Illness Index Severity of Illness Index Severity of Illness Index Biomarkers blood Biomarkers blood Biomarkers blood Cytokines blood Cytokines blood Cytokines blood Acute-On-Chronic Liver Failure blood Acute-On-Chronic Liver Failure blood Acute-On-Chronic Liver Failure blood Acute-On-Chronic Liver Failure etiology Acute-On-Chronic Liver Failure etiology Acute-On-Chronic Liver Failure etiology Acute-On-Chronic Liver Failure genetics Acute-On-Chronic Liver Failure genetics Acute-On-Chronic Liver Failure genetics Health Sciences Medicine Hepatology Liver Disease and Transplantation Life Sciences Immunology and Microbiology Immunology Immune Response and Inflammation Health Sciences Medicine Epidemiology Sepsis Diagnosis and Treatment |
| topic_facet | Medicine Systemic inflammation Cirrhosis White blood cell Internal medicine Inflammation Framingham Risk Score Immune system Gastroenterology Oncology Immunology Disease Medicine Systemic inflammation Cirrhosis White blood cell Internal medicine Inflammation Framingham Risk Score Immune system Gastroenterology Oncology Immunology Aged Aged Aged C-Reactive Protein analysis C-Reactive Protein analysis C-Reactive Protein analysis Female Female Female Humans Humans Humans Inflammation blood Inflammation blood Inflammation blood Inflammation genetics Inflammation genetics Inflammation genetics Leukocyte Count Leukocyte Count Leukocyte Count Liver Cirrhosis blood Liver Cirrhosis blood Liver Cirrhosis blood Liver Cirrhosis complications Liver Cirrhosis complications Liver Cirrhosis complications Liver Cirrhosis genetics Liver Cirrhosis genetics Liver Cirrhosis genetics Male Male Male Middle Aged Middle Aged Middle Aged Severity of Illness Index Severity of Illness Index Severity of Illness Index Biomarkers blood Biomarkers blood Biomarkers blood Cytokines blood Cytokines blood Cytokines blood Acute-On-Chronic Liver Failure blood Acute-On-Chronic Liver Failure blood Acute-On-Chronic Liver Failure blood Acute-On-Chronic Liver Failure etiology Acute-On-Chronic Liver Failure etiology Acute-On-Chronic Liver Failure etiology Acute-On-Chronic Liver Failure genetics Acute-On-Chronic Liver Failure genetics Acute-On-Chronic Liver Failure genetics Health Sciences Medicine Hepatology Liver Disease and Transplantation Life Sciences Immunology and Microbiology Immunology Immune Response and Inflammation Health Sciences Medicine Epidemiology Sepsis Diagnosis and Treatment |
| url | https://pubmed.ncbi.nlm.nih.gov/40011033 https://gut.bmj.com/content/gutjnl/early/2025/02/26/gutjnl-2024-333876.full.pdf https://doi.org/10.1136/gutjnl-2024-333876 https://hdl.handle.net/20.500.15037/1355 |
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