title: From stable disease to acute-on-chronic liver failure: Circulating cytokines are related to prognosis in different stages of cirrhosis.
abstract: Although both pro- and anti-inflammatory circulating cytokines are known to be elevated in liver cirrhosis, its clinical significance is not completely recognized. Our aim was to evaluate the prognostic significance of circulating cytokines interleukin (IL)-6, IL-17 and IL-10 in different stages of cirrhosis.
  
  
  
  This prospective study included two cohorts: (1) stable cirrhosis attended in the Outpatient Clinic (n=118), and (2) subjects hospitalized for acute decompensation (AD) (n=130). Thirty healthy subjects served as control group.
  
  
  
  Patients with cirrhosis exhibited higher levels of cytokines as compared to controls. In stable cirrhosis, during a median follow-up of 17months, liver-related events occurred in 26 patients. Higher IL-10 levels and Child-Pugh B/C were independently associated with reduced event-free survival. In AD cohort, death after 90days of follow-up occurred in 39 patients and was independently associated with ascites, higher IL-6 and model for end-stage liver disease. IL-6 levels also showed higher AUROC than CRP for predicting bacterial infection in the AD cohort (0.831±0.043vs. 0.763±0.048, respectively). IL-17 decreased at third day of hospitalization only in patients who progressed to death. Higher IL-6 levels were observed in acute-on-chronic liver failure (ACLF) patients even in the absence of bacterial infection whereas IL-10 was higher only in subjects with infection-related ACLF. Higher IL-10 and IL-17 levels were associated with progression to death in ACLF.
  
  
  
  The pattern of immune response seems to vary according to the phase of cirrhosis and is related to prognosis, from stable disease to ACLF.
authors.affiliation: Division of Gastroenterology, Federal University of Santa Catarina, Brazil.
authors.forename: Josiane
authors.initials: J
authors.lastname: Fischer
authors.affiliation: Division of Gastroenterology, Federal University of Santa Catarina, Brazil.
authors.forename: Telma Erotides
authors.initials: TE
authors.lastname: Silva
authors.affiliation: Division of Gastroenterology, Federal University of Santa Catarina, Brazil.
authors.forename: Pedro Eduardo
authors.initials: PE
authors.lastname: Soares E Silva
authors.affiliation: Division of Gastroenterology, Federal University of Santa Catarina, Brazil.
authors.forename: Bruno Silveira
authors.initials: BS
authors.lastname: Colombo
authors.affiliation: Division of Gastroenterology, Federal University of Santa Catarina, Brazil.
authors.forename: Mariana Costa
authors.initials: MC
authors.lastname: Silva
authors.affiliation: Department of Clinical Analysis, Federal University of Santa Catarina, Brazil.
authors.forename: Letícia Muraro
authors.initials: LM
authors.lastname: Wildner
authors.affiliation: Department of Clinical Analysis, Federal University of Santa Catarina, Brazil.
authors.forename: Maria Luiza
authors.initials: ML
authors.lastname: Bazzo
authors.affiliation: Department of Clinical Analysis, Federal University of Santa Catarina, Brazil.
authors.forename: Elayne Cristina Morais
authors.initials: EC
authors.lastname: Rateke
authors.affiliation: Department of Clinical Analysis, Federal University of Santa Catarina, Brazil.
authors.forename: Tania Silvia
authors.initials: TS
authors.lastname: Frode
authors.affiliation: Department of Clinical Analysis, Federal University of Santa Catarina, Brazil.
authors.forename: Silvana Vigil de
authors.initials: SV
authors.lastname: Mello
authors.affiliation: Department of Clinical Analysis, Federal University of Santa Catarina, Brazil.
authors.forename: Júlia S
authors.initials: JS
authors.lastname: Rosa
authors.affiliation: Division of Gastroenterology, Federal University of Santa Catarina, Brazil.
authors.forename: Esther Buzaglo
authors.initials: EB
authors.lastname: Dantas-Correa
authors.affiliation: Division of Gastroenterology, Federal University of Santa Catarina, Brazil.
authors.forename: Janaína Luz
authors.initials: JL
authors.lastname: Narciso-Schiavon
authors.affiliation: Division of Gastroenterology, Federal University of Santa Catarina, Brazil. Electronic address: leo-jf@uol.com.br.
authors.forename: Leonardo Lucca
authors.initials: LL
authors.lastname: Schiavon
mesh_terms: D065290:Acute-On-Chronic Liver Failure / Q000097:blood* / Q000175:diagnosis; D000328:Adult; D000368:Aged; D016207:Cytokines / Q000097:blood*; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood* / Q000175:diagnosis; D008875:Middle Aged; D011379:Prognosis
chemical_list: D016207:Cytokines
keywords: Cytokines; Interleukin-10; Interleukin-17; Interleukin-6; Liver cirrhosis