Low sphingosine-1-phosphate plasma levels are predictive for increased mortality in patients with liver cirrhosis

Abstract

Background & aimThe association of circulating sphingosine-1-phosphate (S1P), a bioactive lipid involved in various cellular processes, and related metabolites such as sphinganine-1-phosphate (SA1P) and sphingosine (SPH) with mortality in patients with end-stage liver disease is investigated in the presented study. S1P as a bioactive lipid mediator, is involved in several cellular processes, however, in end-stage liver disease its role is not understood.MethodsThe study cohort consisted of 95 patients with end-stage liver disease and available information on one-year outcome. The median MELD (Model for end-stage liver disease) score was 12.41 (Range 6.43–39.63). The quantification of sphingolipids in citrated plasma specimen was performed after methanolic protein precipitation followed by hydrophilic interaction liquid chromatography and tandem mass spectrometric detection.ResultsS1P and SA1P displayed significant correlations with the MELD score. Patients with circulating S1P levels below the lowest tertile (110.68 ng/ml) showed the poorest one-year survival rate of only 57.1%, whereas one-year survival rate in patients with S1P plasma levels above 165.67 ng/ml was 93.8%. In a multivariate cox regression analysis including platelet counts, concentrations of hemoglobin and MELD score, S1P remained a significant predictor for three-month and one-year mortality.ConclusionsLow plasma S1P concentrations are highly significantly associated with prognosis in end-stage liver disease. This association is independent of the stage of liver disease. Further studies should be performed to investigate S1P, its role in the pathophysiology of liver diseases and its potential for therapeutic interventions.

The Role of S1P and the Related Signaling Pathway in the Development of Tissue Fibrosis

“…Hepatic fibrosis is a sign of performance during the pathogenesis of liver cancer. Recently, a cohort study showed that S1P may be one of markers to estimate the severity of liver disease (Bartels et al, 2017).…”

“…In addition to drug therapy, S1P is also a potential biomarker of some diseases. In a study, S1P was considered to be a potential biomarker for judging the severity of liver diseases (Bartels et al, 2017). However, due to the complexity and high cost during the measure of S1P at present, the clinical application cannot be realized in a short time.…”

Reduced Serum Sphingolipids Constitute a Molecular Signature of Malnutrition in Hospitalized Patients With Decompensated Cirrhosis

“…Other studies have demonstrated low circulating sphingolipid levels in children with severe acute malnutrition that persist even after adequate nutritional stabilization (33). In chronic liver diseases, circulating sphingolipid fall with progressive fibrosis, and low levels of both long-chain ceramides and sphinogsine-1-phosphate were associated with hepatic decompensation and death in cirrhotic subjects (34–36). In the current study, there was a significant overlap in the sphingolipid species associated with both malnutrition and increased MELD-Na.…”

A Novel Perspective on the ApoM-S1P Axis, Highlighting the Metabolism of ApoM and Its Role in Liver Fibrosis and Neuroinflammation

“…Over the last decade S1P has emerged to one of the most pivotal signaling molecules in hepatic tissue regeneration and misguided wound healing ultimately leading to liver fibrosis [ 94 , 95 ]. Per definition, fibrosis is the accumulation of fibrous connective tissue in damaged or inflamed organs resulting in permanent scarring, malfunction and/or death [ 96 , 97 ].…”