Lipopolysaccharide-induced plasma PAI-1 increase does not correlate with PAI-1 synthesised de novo in the liver

Woźnica³

et al. 2021

Preprint

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.

Section: Resultssupporting

confidence: 47%

Section: Pai-1mentioning

confidence: 99%

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

Woźnica³

et al. 2021

Preprint

“…Low speci city of PAI-1 may be a result of many origins and different factors inducing its synthesis. Increase in plasma PAI-1 after LPS-stimulation may be a combined effect of both PAI-1 release from activated platelets and its synthesis associated with PAI-1 gene expression on hepatocytes [29]. The results obtained in our study group may indicate that the activated platelets could play a greater role in an increase in PAI-1 levels, than its hepatic source does.…”

Section: Discussionsupporting

confidence: 46%

“…PAI-1 gene is expressed in liver, endothelial cells, macrophages, adipose tissue, heart and kidney [28]. Increase in plasma PAI-1 after LPS-stimulation may be a combined effect of both PAI-1 release from activated platelets and its synthesis associated with PAI-1 gene expression on hepatocytes [29]. Plasma PAI-1 levels are also strongly related to liver steatosis, what supports the thesis of liver being an important source of circulating PAI-1 [30].…”

Section: Pai-1mentioning

confidence: 99%

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

Woźnica³

et al. 2020

Preprint

Background Sepsis-associated liver dysfunction (SALD) is associated with poor prognosis and an increased mortality in Intensive Care Unit (ICU). Bilirubin is one of the components of Sequential Organ Failure Assessment (SOFA) 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 an 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, 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 Seventy-nine patients were enrolled into the study, and 24 (30,4%) of them developed SALD. PAI-1 with cut-off value of 9 ng/ml was shown to be a good 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). In combination with AST it was also useful in predicting 28-day survival (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 predicts better the 28-day survival, than PAI-1 alone, but due to low cut-off values of AST it might not be clinically significant.

“…The PAI-1 gene is expressed in the liver, endothelial cells, macrophages, adipose tissue, the heart, and kidney [ 28 ]. An increase in plasma PAI-1 after LPS stimulation may be a combined effect of both PAI-1 release from activated platelets and its synthesis associated with PAI-1 gene expression on hepatocytes [ 29 ]. Plasma PAI-1 levels are also strongly related to liver steatosis, which supports the hypothesis that the liver is an important source of circulating PAI-1 [ 30 ].…”

Section: Methodsmentioning

confidence: 99%

The Role of Plasminogen Activator Inhibitor 1 in Predicting Sepsis-Associated Liver Dysfunction: An Observational Study

Janc

et al. 2023

IJERPH

Sepsis-associated liver dysfunction (SALD) is associated with a 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. This study aimed to identify plasma biomarkers that could be used for an early diagnosis of SALD. This prospective, observational study was conducted on a group of 79 patients with sepsis and septic shock treated in the ICU. 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 within 24 h after having developed sepsis/septic shock. Enrolled patients were followed for 14 days for developing SALD and 28 days for overall survival. A total of 24 patients (30.4%) developed SALD. PAI-1 with a cut-off value of 48.7 ng/mL was shown to be a predictor of SALD (AUC = 0.671, sensitivity 87.3%, and specificity 50.0%) and of 28-day survival in patients with sepsis/septic shock (p = 0.001). Measuring PAI-1 serum levels at the onset of sepsis and septic shock may be useful in predicting the development of SALD. This should be verified in multicenter prospective clinical trials.