Serum sphingolipid variations associate with hepatic decompensation and survival in patients with cirrhosis

  • 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.

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Author:Georgios Grammatikos, Nerea Ferreiròs, Oliver WaidmannORCiDGND, Dimitra Bon, Sirkka Schroeter, Alexander Koch, Eva HerrmannORCiD, Stefan ZeuzemORCiDGND, Bernd Kronenberger, Josef Martin PfeilschifterGND
URN:urn:nbn:de:hebis:30:3-390332
DOI:https://doi.org/10.1371/journal.pone.0138130
ISSN:1932-6203
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/26382760
Parent Title (English):PLoS One
Publisher:PLoS
Place of publication:Lawrence, Kan.
Document Type:Article
Language:English
Date of Publication (online):2015/09/18
Date of first Publication:2015/09/18
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2015/12/23
Volume:10
Issue:(9): e0138130
Page Number:15
First Page:1
Last Page:15
Note:
Copyright: © 2015 Grammatikos et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
HeBIS-PPN:374140073
Institutes:Biowissenschaften / Biowissenschaften
Medizin / Medizin
Angeschlossene und kooperierende Institutionen / Senckenbergische Naturforschende Gesellschaft
Biowissenschaften / Institut für Ökologie, Evolution und Diversität
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0