TY  - JOUR
A1  - Mücke, Victoria Therese
A1  - Gerharz, Janis
A1  - Jakobi, Katja
A1  - Thomas, Dominique Jeanette
A1  - Ferreirós Bouzas, Nerea
A1  - Mücke, Marcus Maximilian
A1  - Trötschler, Sven
A1  - Weiler, Nina
A1  - Welker, Martin-Walter
A1  - Zeuzem, Stefan
A1  - Pfeilschifter, Josef
A1  - Grammatikos, Georgios
T1  - Low serum levels of (dihydro-)ceramides reflect liver graft dysfunction in a real-world cohort of patients post liver transplantation
T2  - International journal of molecular sciences
N2  - 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.
KW  - sphingolipids
KW  - orthopic liver transplantation
KW  - graft rejection
KW  - ischemic type biliary lesions
Y1  - 2018
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/47179
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-471792
SN  - 1422-0067
SN  - 1661-6596
N1  - 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).
VL  - 19
IS  - 4, Art. 991
SP  - 1
EP  - 15
PB  - Molecular Diversity Preservation International
CY  - Basel
ER  -