TY - JOUR A1 - Kronenberger, Bernd A1 - Rudloff, Ina A1 - Bachmann, Malte A1 - Brunner, Friederike A1 - Kapper, Lisa A1 - Filmann, Natalie A1 - Waidmann, Oliver A1 - Herrmann, Eva A1 - Pfeilschifter, Josef A1 - Zeuzem, Stefan A1 - Piiper, Albrecht A1 - Mühl, Heiko T1 - Interleukin-22 predicts severity and death in advanced liver cirrhosis: a prospective cohort study T2 - BMC medicine N2 - Background: Interleukin-22 (IL-22), recently identified as a crucial parameter of pathology in experimental liver damage, may determine survival in clinical end-stage liver disease. Systematic analysis of serum IL-22 in relation to morbidity and mortality of patients with advanced liver cirrhosis has not been performed so far. Methods: This is a prospective cohort study including 120 liver cirrhosis patients and 40 healthy donors to analyze systemic levels of IL-22 in relation to survival and hepatic complications. Results: A total of 71% of patients displayed liver cirrhosis-related complications at study inclusion. A total of 23% of the patients died during a mean follow-up of 196 +/- 165 days. Systemic IL-22 was detectable in 74% of patients but only in 10% of healthy donors (P <0.001). Elevated levels of IL-22 were associated with ascites (P = 0.006), hepatorenal syndrome (P <0.0001), and spontaneous bacterial peritonitis (P = 0.001). Patients with elevated IL-22 (>18 pg/ml, n = 57) showed significantly reduced survival compared to patients with regular ([less than or equal to]18 pg/ml) levels of IL-22 (321 days versus 526 days, P = 0.003). Other factors associated with overall survival were high CRP ([greater than or equal to]2.9 mg/dl, P = 0.005, hazard ratio (HR) 0.314, confidence interval (CI) (0.141 to 0.702)), elevated serum creatinine (P = 0.05, HR 0.453, CI (0.203 to 1.012)), presence of liver-related complications (P = 0.028, HR 0.258 CI (0.077 to 0.862)), model of end stage liver disease (MELD) score [greater than or equal to]20 (P = 0.017, HR 0.364, CI (0.159 to 0.835)) and age (P = 0.011, HR 1.047, CI (1.011 to 1.085)). Adjusted multivariate Cox proportional-hazards analysis identified elevated systemic IL-22 levels as independent predictors of reduced survival (P = 0.007, HR 0.218, CI (0.072 to 0.662)). Conclusions: In patients with liver cirrhosis, elevated systemic IL-22 levels are predictive for reduced survival independently from age, liver-related complications, CRP, creatinine and the MELD score. Thus, processes that lead to a rise in systemic interleukin-22 may be relevant for prognosis of advanced liver cirrhosis. KW - Interleukin-22 KW - Liver cirrhosis KW - Liver-related complications KW - Hepatitis KW - Alcoholic liver disease KW - MELD Y1 - 2012 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/26336 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-263362 SN - 1741-7015 N1 - © 2012 Kronenberger et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. VL - 10 IS - 102 PB - London CY - BioMed Central ER -