High serum lipopolysaccharide binding protein is associated with increased mortality in patients with decompensated cirrhosis

• Published in: Liver international Vol. 37; no. 4; pp. 576 - 582
• Main Authors: Agiasotelli, Danai, Alexopoulou, Alexandra, Vasilieva, Larisa, Hadziyannis, Emilia, Goukos, Dimitris, Daikos, George L., Dourakis, Spyros P.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01-04-2017
• Subjects: Acute-Phase Proteins; Aged; Ascitic Fluid - chemistry; Bacteria; Bacterial infections; Bacterial Infections - blood; Bacterial Translocation; Binding; Biomarkers; Carrier Proteins - blood; Cirrhosis; decompensated cirrhosis; Diagnostic systems; Female; Greece; Hepatocytes; Humans; Infections; Intestine; Leukocytes (neutrophilic); lipopolysaccharide binding protein; Lipopolysaccharides; Liver cirrhosis; Liver Cirrhosis - complications; Liver Cirrhosis - mortality; Male; Males; Membrane Glycoproteins - blood; Middle Aged; Mortality; Multivariate Analysis; Patients; Peritonitis; Peritonitis - blood; Peritonitis - microbiology; Permeability; Predictive Value of Tests; predictors of mortality; Prospective Studies; Proteins; Regression analysis; ROC Curve; Severity of Illness Index; Survival Analysis; Translocation; bacterial translocation; decompensated cirrhosis; lipopolysaccharide binding protein; predictors of mortality
• ISSN: 1478-3223; 1478-3231
• DOI: 10.1111/liv.13264

Background & Aims
Lipopolysaccharide‐binding‐protein (LBP) is an acute‐phase‐protein produced by hepatocytes. Changes in LBP are associated with the dynamics of bacterial translocation and intestinal permeability in decompensated cirrhosis (DC). We assessed serum and ascitic‐fluid (AF) LBP and examined their association with mortality in patients with DC.
Methods
Eighty‐eight consecutive patients (73.9% males) underwent thorough diagnostic investigations for infection. LBP (ng/mL) was assessed in serum (N=88) and AF (n=49) by enzyme‐linked‐immunosorbent‐assay and expressed in natural logarithm (ln).
Results
Serum lnLBP was higher in 18 patients with overt infection compared to those without (P<.001). Serum and AF lnLBP 13.49 and 12.11 displayed a very good‐negative‐predictive value of 90% and 95.1% to rule out infection and spontaneous‐bacterial‐peritonitis (SBP), respectively. LBP was higher in serum than in AF (P<.001). Serum and AF LBP levels showed a positive correlation with surrogate markers of inflammation. Patients without overt infection were prospectively followed up. The 90‐day‐mortality rate was 48% and 24.4% in patients with high (≥13.49) and low (<13.49) lnLBP, respectively, (log rank P=0.045). In univariate Cox regression analysis, neutrophils, LBP, MELD score and CRP were predictive of mortality. However, only high LBP (HR 8.1 95%CI 2.0‐31.5, P=0.003) and MELD (HR 1.1 95%CI 1.0‐1.2, P=0.002) were predictive of mortality in multivariate analysis.
Conclusions
Serum and AF LBP concentrations showed a high negative‐predictive‐value to exclude infection and SBP, respectively. High serum LBP was detected in patients without infection at presentation who died during the 90‐day‐follow‐up period. Elevated serum LBP is a marker of short‐term mortality in patients without overt bacterial infection.