Low serum levels of (dihydro-)ceramides reflect liver graft dysfunction in a real-world cohort of patients post liver transplantation

Patients after orthopic liver transplantation (OLT) are at risk of developing graft dysfunction. Sphingolipids (SL’s) have been identified to play a pivotal role in the regulation of hepatocellular apoptosis, inflammatio
Patients after orthopic liver transplantation (OLT) are at risk of developing graft dysfunction. Sphingolipids (SL’s) have been identified to play a pivotal role in the regulation of hepatocellular apoptosis, inflammation and immunity. We aimed to investigate the serum SL profile in a prospective real-world cohort of post-OLT patients. From October 2015 until July 2016, 149 well-characterized post-OLT patients were analyzed. SL’s were assessed in serum probes via Liquid Chromatography/Tandem Mass Spectrometry. Twenty-nine (20%) patients had a biopsy proven graft rejection with decreased C20-ceramide (Cer) (p = 0.042), C18-dihydroceramide (DHC) (p = 0.022) and C24DHC (p = 0.060) levels. Furthermore, C18DHC (p = 0.044) and C24DHC (p = 0.011) were significantly down-regulated in patients with ischemic type biliary lesions (ITBL; n = 15; 10%). One-hundred and thirty-three patients (89%) have so far received tacrolimus as the main immunosuppressive agent with observed elevations of C14Cer (p = 0.052), C18Cer (p = 0.049) and C18:1Cer (p = 0.024). Hepatocellular carcinoma (HCC) pre-OLT was associated with increases in C24:1Cer (p = 0.024) and C24:1DHC (p = 0.024). In this large prospective cross-sectional study of patients, post-OLT serum levels of (very-)long chain (dihydro-)ceramides associate with graft rejection, ITBL, tacrolimus intake and HCC pre-OLT. Hence, serum SL’s may be indicative of graft complications. Further research is necessary to identify their diverse mechanistic role in regulating immunity and inflammation in patients post-OLT.
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Metadaten
Author:Victoria Therese Mücke, Janis Gerharz, Katja Jakobi, Dominique Jeanette Thomas, Nerea Ferreirós Bouzas, Marcus Maximilian Mücke, Sven Trötschler, Nina Weiler, Martin-Walter Welker, Stefan Zeuzem, Josef Martin Pfeilschifter, Georgios Grammatikos
URN:urn:nbn:de:hebis:30:3-471792
DOI:http://dx.doi.org/10.3390/ijms19040991
ISSN:1422-0067
ISSN:1661-6596
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=29587453
Parent Title (English):International journal of molecular sciences
Publisher:Molecular Diversity Preservation International
Place of publication:Basel
Document Type:Article
Language:English
Year of Completion:2018
Date of first Publication:2018/03/26
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2018/09/11
Tag:graft rejection; ischemic type biliary lesions; orthopic liver transplantation; sphingolipids
Volume:19
Issue:4, Art. 991
Pagenumber:15
First Page:1
Last Page:15
Note:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
HeBIS PPN:437752003
Institutes:Medizin
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0

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