The role of Plasminogen Activator Inhibitor 1 in predicting sepsis-associated liver dysfunction: an observational study

Abstract

Background: Sepsis-associated liver dysfunction (SALD) is associated with poor prognosis and increased mortality in the Intensive Care Unit. Bilirubin is one of the components of Sequential Organ Failure Assessment used in Sepsis-3 criteria. Hyperbilirubinemia is a late and non-specific symptom of liver dysfunction. The aim of the study was to identify plasma biomarkers, which could be used for the early diagnosis of SALD.Methods: A single-centre, prospective observational study was conducted in the ICU of Wroclaw University Hospital. Plasma biomarkers - prothrombin time, INR, antithrombin III, bilirubin, aspartate transaminase (AST), alanine transaminase, alkaline phosphatase, gamma glutamyl transferase, albumin, endothelin-1, hepcidin, plasminogen activator inhibitor-1 (PAI-1), thrombin-antithrombin complex and interferon-gamma inducible protein 10 kDa were analysed. Plasma samples were obtained from eligible septic patients within 24 hours after having developed sepsis/septic shock. Enrolled patients were followed for 14 days for developing SALD and 28 days for overall survival.Results: 79 patients were enrolled in the study, and 24 (30.4%) of them developed SALD. PAI-1 with a cut-off value of 9ng/ml was shown to be a predictor of SALD (AUC=0.727, sensitivity 79.2%; specificity 41.8%; accuracy 53.2%) and of 28-day survival in patients with sepsis/septic shock (log rank test, p=0.00091). This was also useful in predicting 28-day survival, in combination with AST (log rank test, p=0.00242).Conclusions: Sepsis-associated hyperbilirubinemia is frequent, but bilirubin is a late and non-specific marker of SALD. Measuring PAI-1 serum levels at the onset of sepsis/ septic shock may be useful in predicting the development of SALD. A combination of PAI-1 and AST better predicts the 28-day survival than PAI-1 alone, but due to the low cut-off values of AST, this might not be clinically significant.