Mücke Victoria T, Maria Schwarzkopf Katharina, Thomas Dominique, Mücke Marcus M, Rüschenbaum Sabrina, Trebicka Jonel, Pfeilschifter Josef, Zeuzem Stefan, Lange Christian M, Grammatikos Georgios
Departement of Internal Medicine 1 University Hospital Frankfurt Goethe University Frankfurt am Main Germany.
Pharmazentrum Frankfurt Institute of Clinical Pharmacology Goethe University Frankfurt am Main Germany.
Hepatol Commun. 2020 Aug 12;4(10):1477-1486. doi: 10.1002/hep4.1561. eCollection 2020 Oct.
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.
鞘氨醇-1-磷酸（S1P）调节多种病理生理过程，包括肝脏再生、血管张力控制和免疫反应。在肝硬化患者中，肝功能急性恶化与高死亡率相关。本研究调查了慢性肝病患者，从代偿期肝硬化（CC）、急性失代偿期（AD）或慢加急性肝衰竭（ACLF），其血清S1P浓度是否与疾病严重程度相关。2013年8月至2017年10月，入住法兰克福大学医院的CC、AD或ACLF患者被纳入我们的肝硬化队列研究。对127例患者的血清样本进行串联质谱分析以评估S1P浓度。我们的研究包括19例CC患者、55例AD患者和51例ACLF患者，年龄在29至76岁之间。我们观察到，随着肝损伤从CC、AD进展到ACLF，S1P显著降低（<0.001）。随着进展到ACLF 3级，S1P水平进一步降低（<0.05），且S1P与终末期肝病模型评分高度负相关（r = -0.508；<0.001）。在多变量分析中，S1P仍然是7天死亡率的独立预测因子，诊断准确性高（曲线下面积，0.874；<0.001）。在慢性肝病患者中，血清S1P水平随着肝病晚期而显著降低，并可预测早期死亡率。由于S1P是内皮完整性和免疫反应的有效调节因子，低S1P水平可能会显著影响进行性多器官功能衰竭。我们的数据证明有必要进一步阐明S1P在ACLF中的诊断和治疗作用。
