title: Systemic inflammation in decompensated cirrhosis: Characterization and role in acute-on-chronic liver failure.
abstract: Acute-on-chronic liver failure (ACLF) in cirrhosis is characterized by acute decompensation (AD), organ failure(s), and high short-term mortality. Recently, we have proposed (systemic inflammation [SI] hypothesis) that ACLF is the expression of an acute exacerbation of the SI already present in decompensated cirrhosis. This study was aimed at testing this hypothesis and included 522 patients with decompensated cirrhosis (237 with ACLF) and 40 healthy subjects. SI was assessed by measuring 29 cytokines and the redox state of circulating albumin (HNA2), a marker of systemic oxidative stress. Systemic circulatory dysfunction (SCD) was estimated by plasma renin (PRC) and copeptin (PCC) concentrations. Measurements were performed at enrollment (baseline) in all patients and sequentially during hospitalization in 255. The main findings of this study were: (1) Patients with AD without ACLF showed very high baseline levels of inflammatory cytokines, HNA2, PRC, and PCC. Patients with ACLF showed significantly higher levels of these markers than those without ACLF; (2) different cytokine profiles were identified according to the type of ACLF precipitating event (active alcoholism/acute alcoholic hepatitis, bacterial infection, and others); (3) severity of SI and frequency and severity of ACLF at enrollment were strongly associated. The course of SI and the course of ACLF (improvement, no change, or worsening) during hospitalization and short-term mortality were also strongly associated; and (4) the strength of association of ACLF with SI was higher than with SCD.
  
  
  
  These data support SI as the primary driver of ACLF in cirrhosis. (Hepatology 2016;64:1249-1264).
authors.affiliation: Department of Biochemistry and Molecular Genetics, Hospital Clínic, IDIBAPS and CIBERehd, Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Clària
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Rudolf E
authors.initials: RE
authors.lastname: Stauber
authors.affiliation: Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Minneke J
authors.initials: MJ
authors.lastname: Coenraad
authors.affiliation: Inserm, U1149, Centre de Recherche sur l'Inflammation (CRI), UMRS1149; Université Paris Diderot-Paris 7, Département Hospitalo-Universitaire (DHU) UNITY; Service d'Hépatologie, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Laboratoire d'Excellence Inflamex, ComUE Sorbonne Paris Cité, Paris, France.
authors.forename: Richard
authors.initials: R
authors.lastname: Moreau
authors.affiliation: Liver Failure Group, Institute for Liver Disease Health, University College London, Royal Free Hospital, London, United Kingdom.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Jalan
authors.affiliation: EF-CLIF and EASL-CLIF Consortium, Barcelona, Spain.
authors.forename: Marco
authors.initials: M
authors.lastname: Pavesi
authors.affiliation: EF-CLIF and EASL-CLIF Consortium, Barcelona, Spain.
authors.forename: Àlex
authors.initials: À
authors.lastname: Amorós
authors.affiliation: Department of Biochemistry and Molecular Genetics, Hospital Clínic, IDIBAPS and CIBERehd, Barcelona, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Titos
authors.affiliation: Department of Biochemistry and Molecular Genetics, Hospital Clínic, IDIBAPS and CIBERehd, Barcelona, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Alcaraz-Quiles
authors.affiliation: Institute of Physiological Chemistry, Medical University of Graz, Graz, Austria.
authors.forename: Karl
authors.initials: K
authors.lastname: Oettl
authors.affiliation: Department of Biochemistry and Molecular Genetics, Hospital Clínic, IDIBAPS and CIBERehd, Barcelona, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Morales-Ruiz
authors.affiliation: Unit of Internal Medicine and Hepatology, Department of Medicine, DIMED, University of Padova, Padova, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Angeli
authors.affiliation: Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Domenicali
authors.affiliation: Division of Gastroenterology and Hepatology, San Giovanni Battista Hospital, Torino, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Alessandria
authors.affiliation: Department of Medicine II, University Hospital LMU Munich, Liver Center Munich, Munich, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Gerbes
authors.affiliation: Kings College London, London, United Kingdom.
authors.forename: Julia
authors.initials: J
authors.lastname: Wendon
authors.affiliation: University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium.
authors.forename: Frederik
authors.initials: F
authors.lastname: Nevens
authors.affiliation: Department of Internal Medicine I, University of Bonn, Bonn, Germany.
authors.forename: Jonel
authors.initials: J
authors.lastname: Trebicka
authors.affiliation: University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium.
authors.forename: Wim
authors.initials: W
authors.lastname: Laleman
authors.affiliation: Hôpital Paul Brousse, Université Paris-Sud, Villejuif, France.
authors.forename: Faouzi
authors.initials: F
authors.lastname: Saliba
authors.affiliation: J.W. Goethe University Hospital, Frankfurt, Germany.
authors.forename: Tania M
authors.initials: TM
authors.lastname: Welzel
authors.affiliation: Hospital Ramón y Cajal, Madrid, Spain.
authors.forename: Agustin
authors.initials: A
authors.lastname: Albillos
authors.affiliation: Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Thierry
authors.initials: T
authors.lastname: Gustot
authors.affiliation: University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Benten
authors.affiliation: Inserm, U1149, Centre de Recherche sur l'Inflammation (CRI), UMRS1149; Université Paris Diderot-Paris 7, Département Hospitalo-Universitaire (DHU) UNITY; Service d'Hépatologie, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Laboratoire d'Excellence Inflamex, ComUE Sorbonne Paris Cité, Paris, France.
authors.forename: François
authors.initials: F
authors.lastname: Durand
authors.affiliation: Liver Unit, Hospital Clínic, IDIBAPS and CIBERehd, Barcelona, Spain. pgines@clinic.ub.es.
authors.forename: Pere
authors.initials: P
authors.lastname: Ginès
authors.affiliation: Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Bernardi
authors.affiliation: EF-CLIF and EASL-CLIF Consortium, Barcelona, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Arroyo
mesh_terms: D065290:Acute-On-Chronic Liver Failure / Q000097:blood / Q000150:complications*; D015415:Biomarkers / Q000097:blood; D016207:Cytokines / Q000097:blood; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000209:etiology*; D008103:Liver Cirrhosis / Q000097:blood / Q000150:complications*
chemical_list: D015415:Biomarkers; D016207:Cytokines