BACKGROUND AND AIMS
Bacterial infection (BI) is a common event in the natural history of cirrhosis, often requiring hospitalisation due to hepatic and extra-hepatic organ dysfunction. Diagnostic criteria for severe infection and sepsis currently adopted in the general population display suboptimal accuracy in patients with cirrhosis.1 Common serum biomarkers such as C-reactive protein (CRP), white blood cells (WBC), and procalcitonin (PCT) are often inaccurate in the early diagnosis of BI in cirrhosis. Presepsin (PSP), a 13 kDa fragment of CD14, is released into the blood upon the activation of monocytes in response to BI and has been evaluated as a promising diagnostic sepsis biomarker and prognostic tool in different populations.2,3 This study aimed to prospectively evaluate PSP in a cohort of hospitalised patients with cirrhosis, with and without BI, to investigate its diagnostic accuracy in comparison with other commonly used biomarkers (i.e., CRP, PCT, and WBC); and to evaluate its prognostic role in short-term mortality.
MATERIALS AND METHODS
All cirrhotic patients admitted at Padua University Hospital between 2016 and 2019 were consecutively enrolled. Patients aged <18 or >80 years and with a prior solid organ transplant were excluded. For each patient, PSP was measured at hospitalisation by Pathfast™ technique (chemiluminescent enzyme immune assay) and its diagnostic accuracy was compared with that of CRP, PCT, and WBC. The 28-day outcome of each patient was evaluated considering liver transplantation as a competing event. Predictors of mortality were assessed with multivariable analysis.
Two-hundred and seventy-eight patients with cirrhosis were prospectively enrolled (males: 179; females: 99; mean±standard deviation [SD] age: 56±11 years; alcohol-related disease: 47.5%), for a total of 448 hospitalisations. The mean±SD Child–Pugh and Model for End-Stage Liver Disease (MELD) score at admission was 9.3±2.5 and 18±8, respectively, whereas 22.5% patients fulfilled criteria of acute-on-chronic liver failure. BI occurred in 28.3% of cases at hospitalisation, with the lower respiratory tract and blood being the most common sources (24% and 19%, respectively). In the whole cohort, the mean±SD PSP value was 1,620±3,014 ng/L. There was a correlation between serum PSP values and severity of underlying liver disease according to Child–Pugh class (p=0.001). Furthermore, serum PSP values were significantly higher in patients with BI than in those without (p=0.001). When comparing patients with similar underlying liver dysfunction, PSP significantly varied according to infectious status in those belonging to Child–Pugh A class (p<0.001), but not among patients with Child–Pugh B and C class (each p=0.06; Figure 1). A PSP cut-off value of 752 ng/L was able to retrieve the best diagnostic accuracy for BI, displaying an area under the curve–receiver operating characteristic equal to 0.685 (95% confidence interval [CI]: 0.63–0.73), with a sensitivity and specificity equal to 66.1% (95% CI: 57.2–74.4) and 63.2% (95% CI: 57.7–68.5), respectively. The diagnostic accuracy of PSP was lower than that of CRP (p=0.002), similar to that of PCT (p=0.18), and better than that of WBC (p=0.006). The short-term mortality was 13.8% in the whole cohort and was significantly higher among patients with BI at hospitalisation than in those without at competing risks analysis (p<0.001). At multivariate analysis, age, acute-on-chronic liver failure at hospitalisation, PSP (hazard ratio: 2.37; 95% CI: 1.29–4.34), but not CRP nor BI, were independent predictors of short-term mortality.
Hospitalised patients with cirrhosis had high values of serum PSP. It seemed to be influenced by the severity of underlying liver disease and displayed a diagnostic accuracy lower than that of CRP, but equal to PCT, suggesting a possible role in infection monitoring. PSP was an independent predictor of short-term mortality, reinforcing the role of a proinflammatory state in decompensated cirrhosis.