Serum Sphingosine-1-Phosphate Is Decreased in Patients With Acute-on-Chronic Liver Failure and Predicts Early Mortality.

Sphingosine-1-phosphate (S1P) regulates pathophysiological processes, including liver regeneration, vascular tone control, and immune response. In patients with liver cirrhosis, acute deterioration of liver function is associated with high mortality rates. The present study investigated whether serum S1P concentrations are associated with disease severity in patients with chronic liver disease from compensated cirrhosis (CC), acute decompensation (AD), or acute-on-chronic liver failure (ACLF). From August 2013 to October 2017, patients who were admitted to the University Hospital Frankfurt with CC, AD, or ACLF were enrolled in our cirrhosis cohort study. Tandem mass spectrometry was performed on serum samples of 127 patients to assess S1P concentration. Our study comprised 19 patients with CC, 55 with AD, and 51 with ACLF, aged 29 to 76 years. We observed a significant decrease of S1P according to advanced liver injury from CC and AD up to ACLF ( < 0.001). S1P levels further decreased with progression to ACLF grade 3 ( < 0.05), and S1P highly inversely correlated with the Model for End-Stage Liver Disease score ( = -0.508;  < 0.001). In multivariate analysis, S1P remained an independent predictor of 7-day mortality with high diagnostic accuracy (area under the curve, 0.874;  < 0.001). In patients with chronic liver disease, serum S1P levels dramatically decreased with advanced stages of liver disease and were predictive of early mortality. Because S1P is a potent regulator of endothelial integrity and immune response, low S1P levels may significantly influence progressive multiorgan failure. Our data justify further elucidation of the diagnostic and therapeutic role of S1P in ACLF.