title: Interleukin-22 predicts severity and death in advanced liver cirrhosis: a prospective cohort study.
abstract: 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 (≤18 pg/ml) levels of IL-22 (321 days versus 526 days, P = 0.003). Other factors associated with reduced overall survival were high CRP (≥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 ≥20 (P = 0.017, HR 0.364, CI (0.159 to 0.835)) and age (P = 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 (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.
authors.affiliation: Medizinische Klinik 1, Klinikum der J.W. Goethe Universität, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany. bernd.kronenberger@email.de
authors.forename: Bernd
authors.initials: B
authors.lastname: Kronenberger
authors.forename: Ina
authors.initials: I
authors.lastname: Rudloff
authors.forename: Malte
authors.initials: M
authors.lastname: Bachmann
authors.forename: Friederike
authors.initials: F
authors.lastname: Brunner
authors.forename: Lisa
authors.initials: L
authors.lastname: Kapper
authors.forename: Natalie
authors.initials: N
authors.lastname: Filmann
authors.forename: Oliver
authors.initials: O
authors.lastname: Waidmann
authors.forename: Eva
authors.initials: E
authors.lastname: Herrmann
authors.forename: Josef
authors.initials: J
authors.lastname: Pfeilschifter
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.forename: Albrecht
authors.initials: A
authors.lastname: Piiper
authors.forename: Heiko
authors.initials: H
authors.lastname: Mühl
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007378:Interleukins / Q000097:blood*; D008103:Liver Cirrhosis / Q000175:diagnosis* / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D044967:Serum / Q000737:chemistry; D016019:Survival Analysis; D015854:Up-Regulation; D000097043:Interleukin-22
chemical_list: D015415:Biomarkers; D007378:Interleukins; D000097043:Interleukin-22