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Open AccessArticle

Low Serum Levels of (Dihydro-)Ceramides Reflect Liver Graft Dysfunction in a Real-World Cohort of Patients Post Liver Transplantation

1
Universitätsklinikum Frankfurt, Medizinische Klinik 1, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany
2
Pharmazentrum Frankfurt, Institut für Allgemeine Pharmakologie und Toxikologie, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany
3
Institut für Klinische Pharmakologie und Toxikologie, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2018, 19(4), 991; https://doi.org/10.3390/ijms19040991
Received: 28 February 2018 / Revised: 19 March 2018 / Accepted: 21 March 2018 / Published: 26 March 2018
(This article belongs to the Special Issue Sphingolipids: Signals and Disease)
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. View Full-Text
Keywords: sphingolipids; orthopic liver transplantation; graft rejection; ischemic type biliary lesions sphingolipids; orthopic liver transplantation; graft rejection; ischemic type biliary lesions
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Mücke, V.T.; Gerharz, J.; Jakobi, K.; Thomas, D.; Ferreirós Bouzas, N.; Mücke, M.M.; Trötschler, S.; Weiler, N.; Welker, M.-W.; Zeuzem, S.; Pfeilschifter, J.; Grammatikos, G. Low Serum Levels of (Dihydro-)Ceramides Reflect Liver Graft Dysfunction in a Real-World Cohort of Patients Post Liver Transplantation. Int. J. Mol. Sci. 2018, 19, 991.

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