Increased Serum Soluble Urokinase Plasminogen Activator Receptor Predicts Short-Term Outcome in Patients with Hepatitis B-Related Acute-on-Chronic Liver Failure

Abstract

Aims. Soluble urokinase plasminogen activator receptor (suPAR) reflects the immune activation in circumstances of inflammation and infection. It has been considered as a risk biomarker associated with poor outcome in various low-grade inflammation and infectious diseases. The study is aimed at investigating whether suPAR has a predictive value with short-term survival in patients with hepatitis B-related acute-on-chronic liver failure (HB-ACLF). Methods. Serum suPAR expression was compared among patients with different states of chronic hepatitis B virus infection. Sixty HB-ACLF patients were recruited as the training cohort and followed up for 90 days. Serum suPAR level and the clinical relevance with short-term outcome were investigated. The temporal dynamics of suPAR were evaluated in 50 HB-ACLF patients with available serum sequentially at baseline, week 2 and week 4. Another 167 HB-ACLF patients were enrolled to validate the predictive value of suPAR with respect to the prognosis. Results. Serum suPAR level was significantly increased in HB-ACLF patients compared to non-ACLF patients. In the training set of HB-ACLF, we observed higher suPAR level, INR, MELD score, and more complications in nonsurvivors than survivors. Longitudinal analysis revealed an increased trend of suPAR level in nonsurvivors during week 0 to week 4 and the modest decline in survivors. It showed that the synchronous suPAR level was higher in nonsurvivors at all indicated time points. Elevated suPAR level at baseline was identified as a strong predictor of a 90-day mortality of HB-ACLF patients. It was confirmed suPAR>16.26 ng/ml had a positive predictive value of 72.22% and a negative predictive value of 77.88% for poor outcome in the validation cohort. Conclusions. Serum suPAR level increases significantly in HB-ACLF patients and associated with a 90-day mortality. It suggests that suPAR might be a potential biomarker to predict the prognosis of HB-ACLF patients.

Soluble Urokinase Plasminogen Activator Receptor (suPAR) Independently Predicts Severity and Length of Hospitalisation in Patients With COVID-19

“…Besides this, the significance of elevated suPAR levels in viral infections such as human immunodeficiency virus, hepatitis B virus, hepatitis C virus, and hantavirus, has been established before the SARS-CoV-2 pandemic. Like its importance in COVID-19, elevated suPAR was demonstrated to significantly correlate with severity and mortality in these conditions (51)(52)(53)(54)(55).…”

Comparison of C-reactive protein with distinct hyperinflammatory biomarkers in association with COVID-19 severity, mortality and SARS-CoV-2 variants

“…During inflammation, uPAR is cleaved and the soluble form, named suPAR, is released into circulation, and acting as a "damage-associated molecular pattern" (DAMP), it exerts local vascular inflammation or distal immune effects (26,43). Elevated suPAR concentrations have been reported in other viral infections caused by hepatitis C and B viruses, HIV or Hantavirus, where it showed correlation with disease severity and mortality (44)(45)(46)(47). SuPAR was also shown to be a discriminator of COVID-19 severity and a predictor of hospitalization time, findings which we have confirmed in our study (27)(28)(29).…”

suPAR to Risk-Stratify Patients With Malaria

“…The prognostic value of suPAR has previously been documented in infectious diseases of variable origin (bacterial, viral, and parasitic) including tuberculosis, bacteremia and/or sepsis, meningitis, hepatitis B and C, HIV-1, hemorrhagic fever, hantavirus, malaria, and most recently coronavirus disease 2019 (COVID-19) (63)(64)(65)(66)(67)(68)(69)(70)(71)(72). Across multiple infectious diseases, suPAR levels are elevated and predict the severity of illness and poor clinical outcomes.…”