Interleukin-22 predicts severity and death in advanced liver cirrhosis: a prospective cohort study

• Main Authors: Kronenberger Bernd, Rudloff Ina, Bachmann Malte, Brunner Friederike, Kapper Lisa, Filmann Natalie, Waidmann Oliver, Herrmann Eva, Pfeilschifter Josef, Zeuzem Stefan, Piiper Albrecht, Mühl Heiko
• Format: Article
• Language: English
• Published: BMC 2012-09-01
• Series: BMC Medicine
• Subjects: Interleukin-22; Liver cirrhosis; Liver-related complications; Hepatitis; Alcoholic liver disease; MELD
• Online Access: http://www.biomedcentral.com/1741-7015/10/102

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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 (<it>P </it>< 0.001). Elevated levels of IL-22 were associated with ascites (<it>P </it>= 0.006), hepatorenal syndrome (<it>P </it>< 0.0001), and spontaneous bacterial peritonitis (<it>P </it>= 0.001). Patients with elevated IL-22 (>18 pg/ml, n = 57) showed significantly reduced survival compared to patients with regular (≤18 pg/ml) levels of IL-22 (321 days <it>versus </it>526 days, <it>P </it>= 0.003). Other factors associated with reduced overall survival were high CRP (≥2.9 mg/dl, <it>P </it>= 0.005, hazard ratio (HR) 0.314, confidence interval (CI) (0.141 to 0.702)), elevated serum creatinine (<it>P </it>= 0.05, HR 0.453, CI (0.203 to 1.012)), presence of liver-related complications (<it>P </it>= 0.028, HR 0.258, CI (0.077 to 0.862)), model of end stage liver disease (MELD) score ≥20 (<it>P </it>= 0.017, HR 0.364, CI (0.159 to 0.835)) and age (<it>P </it>= 0.011, HR 0.955, CI (0.922 to 0.989)). Adjusted multivariate Cox proportional-hazards analysis identified elevated systemic IL-22 levels as independent predictors of reduced survival (<it>P </it>= 0.007, HR 0.218, CI (0.072 to 0.662)).</p> <p>Conclusions</p> <p>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.</p>