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


METHODS
The 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.


RESULTS
S1P 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.


CONCLUSIONS
Low 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.
Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnosis, University Hospital Leipzig, Leipzig, Germany.
Susen
S
Becker
Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnosis, University Hospital Leipzig, Leipzig, Germany.
Benedict
B
Kinny-Köster
Department of Visceral, Vascular, Thoracic and Transplant Surgery, University Hospital Leipzig, Leipzig, Germany.
Michael
M
Bartels
Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.|LIFE - Leipzig Research Center for Civilization Diseases, University Hospital Leipzig, Leipzig, Germany.
Markus
M
Scholz
Department of Visceral, Vascular, Thoracic and Transplant Surgery, University Hospital Leipzig, Leipzig, Germany.
Daniel
D
Seehofer
Department of Gastroenterology and Rheumatology, University of Leipzig, Leipzig, Germany.
Thomas
T
Berg
Department of Gastroenterology and Rheumatology, University of Leipzig, Leipzig, Germany.
Cornelius
C
Engelmann
Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnosis, University Hospital Leipzig, Leipzig, Germany.|LIFE - Leipzig Research Center for Civilization Diseases, University Hospital Leipzig, Leipzig, Germany.
Joachim
J
Thiery
Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnosis, University Hospital Leipzig, Leipzig, Germany.|LIFE - Leipzig Research Center for Civilization Diseases, University Hospital Leipzig, Leipzig, Germany.
Uta
U
Ceglarek
Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnosis, University Hospital Leipzig, Leipzig, Germany.
Thorsten
http://orcid.org/0000-0003-0523-3113
T
Kaiser
D000328:Adult; D000368:Aged; D002853:Chromatography, Liquid; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood* / Q000401:mortality*; D017093:Liver Failure / Q000097:blood* / Q000401:mortality*; D008246:Lysophospholipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000097:blood; D015996:Survival Rate; D053719:Tandem Mass Spectrometry; D055815:Young Adult
D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D013110:Sphingosine