title: Serum Sphingolipid Variations Associate with Hepatic Decompensation and Survival in Patients with Cirrhosis.
abstract: BACKGROUND
  Sphingolipids constitute bioactive molecules with functional implications in liver homeostasis. Particularly, ablation of very long chain ceramides in a knockout mouse model has been shown to cause a severe hepatopathy.
  
  
  METHODS
  We aimed to evaluate the serum sphingolipid profile of 244 patients with cirrhosis prospectively followed for a median period of 228±217 days via mass spectrometry.
  
  
  RESULTS
  We thereby observed a significant decrease of long and very long chain ceramides, particularly of C24ceramide, in patients with increasing severity of cirrhosis (p<0.001). Additionally, hydropic decompensation, defined by clinical presentation of ascites formation, was significantly correlated to low C24ceramide levels (p<0.001) while a significant association to hepatic decompensation and poor overall survival was observed for low serum concentrations of C24ceramide (p<0.001) as well. Multivariate analysis further identified low serum C24ceramide to be independently associated to overall survival (standard beta = -0.001, p = 0.022).
  
  
  CONCLUSIONS
  In our current analysis serum levels of very long chain ceramides show a significant reciprocal correlation to disease severity and hepatic decompensation and are independently associated with overall survival in patients with cirrhosis. Serum sphingolipid metabolites and particularly C24ceramide may constitute novel molecular targets of disease severity, hepatic decompensation and overall prognosis in cirrhosis and should be further evaluated in basic research studies.
authors.affiliation: Pharmazentrum Frankfurt, Institut für Allgemeine Pharmakologie und Toxikologie, Frankfurt am Main, Germany; Goethe University Hospital, Medizinische Klinik 1, Frankfurt am Main, Germany.
authors.forename: Georgios
authors.initials: G
authors.lastname: Grammatikos
authors.affiliation: Pharmazentrum Frankfurt, Institut für klinische Pharmakologie, Goethe University Hospital, Frankfurt am Main, Germany.
authors.forename: Nerea
authors.initials: N
authors.lastname: Ferreiròs
authors.affiliation: Goethe University Hospital, Medizinische Klinik 1, Frankfurt am Main, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Waidmann
authors.affiliation: Goethe University, Department of Medicine, Institute of Biostatistics and Mathematical Modelling, Frankfurt am Main, Germany.
authors.forename: Dimitra
authors.initials: D
authors.lastname: Bon
authors.affiliation: Pharmazentrum Frankfurt, Institut für Allgemeine Pharmakologie und Toxikologie, Frankfurt am Main, Germany; Goethe University Hospital, Medizinische Klinik 1, Frankfurt am Main, Germany.
authors.forename: Sirkka
authors.initials: S
authors.lastname: Schroeter
authors.affiliation: Pharmazentrum Frankfurt, Institut für Allgemeine Pharmakologie und Toxikologie, Frankfurt am Main, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Koch
authors.affiliation: Goethe University, Department of Medicine, Institute of Biostatistics and Mathematical Modelling, Frankfurt am Main, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Herrmann
authors.affiliation: Goethe University Hospital, Medizinische Klinik 1, Frankfurt am Main, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.affiliation: Goethe University Hospital, Medizinische Klinik 1, Frankfurt am Main, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Kronenberger
authors.affiliation: Pharmazentrum Frankfurt, Institut für Allgemeine Pharmakologie und Toxikologie, Frankfurt am Main, Germany.
authors.forename: Josef
authors.initials: J
authors.lastname: Pfeilschifter
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002518:Ceramides / Q000097:blood; D005260:Female; D006801:Humans; D008099:Liver / Q000503:physiopathology*; D008103:Liver Cirrhosis / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D013107:Sphingolipids / Q000097:blood*; D016019:Survival Analysis
chemical_list: D002518:Ceramides; D013107:Sphingolipids