title: Soluble urokinase plasminogen activator receptor is compartmentally regulated in decompensated cirrhosis and indicates immune activation and short-term mortality.
abstract: OBJECTIVE
  Patients with decompensated cirrhosis are susceptible to bacterial infections, which are associated with organ failure and a high mortality rate. Reliable biomarkers are needed to identify patients who require intensified treatment. Our objective was to study the regulation and prognostic relevance of elevated concentrations of soluble urokinase plasminogen activator receptor (suPAR) in patients with advanced cirrhosis.
  
  
  METHODS
  We examined the associations between serum and ascitic fluid (AF) suPAR and liver function, bacterial infection, and short-term mortality in 162 consecutive patients with decompensated cirrhosis undergoing diagnostic paracentesis in a tertiary health care centre in Germany.
  
  
  METHODS
  Twenty-eight-day mortality.
  
  
  RESULTS
  Circulating suPAR levels were increased in patients with decompensated cirrhosis and correlated with the severity of liver dysfunction and systemic inflammation but were not indicative of bacterial infection. Circulating suPAR levels >14.4 ng mL(-1) predicted 28-day mortality, even after adjustment for liver function and confounders [HR = 3.05 (1.35-6.90); P = 0.0076] equal to the MELD score (AUC = 0.71; 95% CI = 0.61-0.81; P < 0.001). Cut-off levels derived from cohorts without liver disease were not applicable due to the low specificity. AF suPAR levels were elevated during spontaneous bacterial peritonitis (SBP), but not during episodes in which bacteria or bacterial DNA was translocated into the ascites. AF suPAR levels correlated poorly with systemic suPAR but were associated with a more severe course of SBP and a worse outcome. In vitro experiments revealed that monocytes, and to a lesser extent neutrophils, secrete suPAR after Toll-like-receptor ligation, which led to rapid urokinase plasminogen activator receptor cleavage followed by increased synthesis.
  
  
  CONCLUSIONS
  Blood and ascitic suPAR levels provide distinct, but relevant prognostic information on the severity of complications in patients with end-stage liver disease.
authors: Department of Medicine III, University Hospital Aachen, Aachen, Germany.
authors: H W
authors: HW
authors: Zimmermann
authors: P A
authors: PA
authors: Reuken
authors: A
authors: A
authors: Koch
authors: M
authors: M
authors: Bartneck
authors: D H
authors: DH
authors: Adams
authors: C
authors: C
authors: Trautwein
authors: A
authors: A
authors: Stallmach
authors: F
authors: F
authors: Tacke
authors: T
authors: T
authors: Bruns
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001202:Ascitic Fluid / Q000378:metabolism*; D001424:Bacterial Infections / Q000378:metabolism* / Q000382:microbiology; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D004927:Escherichia coli Infections / Q000378:metabolism; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000276:immunology / Q000378:metabolism* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D019152:Paracentesis; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D055293:Receptors, Urokinase Plasminogen Activator / Q000097:blood / Q000378:metabolism*; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D055293:Receptors, Urokinase Plasminogen Activator