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, 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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Author:Victoria Therese MückeORCiDGND, Janis Gerharz, Katja Jakobi, Dominique Jeanette ThomasORCiDGND, Nerea Ferreirós BouzasORCiDGND, Marcus Maximilian MückeORCiDGND, Sven Trötschler, Nina Weiler, Martin-Walter WelkerGND, Stefan ZeuzemORCiDGND, Josef PfeilschifterGND, Georgios Grammatikos
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/29587453
Parent Title (English):International journal of molecular sciences
Publisher:Molecular Diversity Preservation International
Place of publication:Basel
Document Type:Article
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
Issue:4, Art. 991
Page Number:15
First Page:1
Last Page:15
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).
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0