From stable disease to acute-on-chronic liver failure: Circulating cytokines are related to prognosis in different stages of cirrhosis

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INTRODUCTIONAlthough 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.METHODSThis 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.RESULTSPatients with cirrhosis exhibited higher levels of cytokines as compared to controls. In stable cirrhosis, during a median follow-up of 17 months, 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 90 days 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 ± 0.043 vs. 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.CONCLUSIONSThe pattern of immune response seems to vary according to the phase of cirrhosis and is related to prognosis, from stable disease to ACLF.HIGHLIGHTSCirculating interleukin (IL)-6, IL-10 and IL-17 were evaluated in cirrhosis.In stable cirrhosis, higher IL-10 levels were associated with worse prognosis.In decompensated cirrhosis, higher circulating IL-6 was related to mortality.IL-6 levels outperformed C-reactive protein for diagnosis of bacterial infections.In ACLF, a stronger anti-inflammatory response was related to death.

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