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

• Published in: International journal of molecular sciences 2018-03, Vol.19 (4), p.991
• Main Authors: Mücke, Victoria Therese, Gerharz, Janis, Jakobi, Katja, Thomas, Dominique, Ferreirós Bouzas, Nerea, Mücke, Marcus Maximilian, Trötschler, Sven, Weiler, Nina, Welker, Martin-Walter, Zeuzem, Stefan, Pfeilschifter, Josef, Grammatikos, Georgios
• Format: Article
• Language: English
• Subjects: graft rejection; ischemic type biliary lesions; orthopic liver transplantation; sphingolipids
• ISSN: 1422-0067; 1422-0067
• DOI: 10.3390/ijms19040991

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) ( = 0.042), C18-dihydroceramide (DHC) ( = 0.022) and C24DHC ( = 0.060) levels. Furthermore, C18DHC ( = 0.044) and C24DHC ( = 0.011) were significantly down-regulated in patients with ischemic type biliary lesions (ITBL; = 15; 10%). One-hundred and thirty-three patients (89%) have so far received tacrolimus as the main immunosuppressive agent with observed elevations of C14Cer ( = 0.052), C18Cer ( = 0.049) and C18:1Cer ( = 0.024). Hepatocellular carcinoma (HCC) pre-OLT was associated with increases in C24:1Cer ( = 0.024) and C24:1DHC ( = 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.