title: Characterization of Inflammatory Response in Acute-on-Chronic Liver Failure and Relationship with Prognosis.
abstract: ACLF is characterized by a systemic inflammatory response, but the cytokines involved in this process have not been well studied. The aim of this study was to characterize the systemic inflammatory response in patients with cirrhosis and ACLF and its relationship with prognosis. Fifty-five patients with cirrhosis, 26 with ACLF, were studied prospectively. Systemic inflammatory response was analyzed by measuring a large array of plasma cytokines by using a multiplex kit. A principal component analysis show noticeable differences between ACLF and decompensated cirrhosis without ACLF. Patients with ACLF had significant abnormal levels of 12 cytokines compared to those without ACLF, including: VCAM-1, VEGF-A, Fractalkine, MIP-1α, Eotaxin, IP-10, RANTES, GM-CSF, IL-1β, IL-2, ICAM-1, and MCP-1. Cytokines showing the most marked relationship with ACLF were VCAM-1 and VEGF-A (AUCROC 0.77; p = 0.001). There was a significant relationship between some of inflammatory mediators and 3-month mortality, particularly VCAM-1, ICAM-1, and GM-CSF (AUCROC>0.7; p < 0.05). Functional Enrichment Analysis showed that inflammatory markers differentially expressed in ACLF patients were enriched in leukocyte migration, particularly monocytes and macrophages, and chemotaxis pathways. In conclusion, ACLF is characterized by a marked inflammatory reaction with activation of mediators of adhesion and migration of leukocytes. The intensity of the inflammatory reaction correlates with prognosis.
authors: Liver Unit, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain.|Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Spain.
authors: Cristina
authors: C
authors: Solé
authors: Liver Unit, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain.|Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Spain.
authors: Elsa
authors: E
authors: Solà
authors: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Spain.|Biochemistry and Molecular Genetics Department, Hospital Clínic de Barcelona, Barcelona, Spain.
authors: Manuel
authors: M
authors: Morales-Ruiz
authors: Bioinformatics Core Facility, IDIBAPS-CEK, Hospital Clínic, University de Barcelona, Spain.
authors: Guerau
authors: G
authors: Fernàndez
authors: Liver Unit, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain.|Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Spain.
authors: Patricia
authors: P
authors: Huelin
authors: Liver Unit, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain.|Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Spain.
authors: Isabel
authors: I
authors: Graupera
authors: Liver Unit, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain.|Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Spain.
authors: Rebeca
authors: R
authors: Moreira
authors: Liver Unit, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain.|Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Spain.
authors: Gloria
authors: G
authors: de Prada
authors: Liver Unit, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain.|Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Spain.
authors: Xavier
authors: X
authors: Ariza
authors: Liver Unit, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain.|Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Spain.
authors: Elisa
authors: E
authors: Pose
authors: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.|Facultat de Medicina i Ciències de la Salut, University of Barcelona, Barcelona, Spain.
authors: Núria
authors: N
authors: Fabrellas
authors: Bioinformatics Core Facility, IDIBAPS-CEK, Hospital Clínic, University de Barcelona, Spain.
authors: Susana G
authors: SG
authors: Kalko
authors: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Spain.|Biochemistry and Molecular Genetics Department, Hospital Clínic de Barcelona, Barcelona, Spain.
authors: Wladimiro
authors: W
authors: Jiménez
authors: Liver Unit, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain.|Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Spain.
authors: Pere
authors: P
authors: Ginès
mesh_terms: D065290:Acute-On-Chronic Liver Failure / Q000097:blood* / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D002448:Cell Adhesion / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D016207:Cytokines / Q000097:blood*; D005260:Female; D005355:Fibrosis / Q000097:blood / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000503:physiopathology; D008297:Male; D011379:Prognosis
chemical_list: D015415:Biomarkers; D016207:Cytokines