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 Mar 26;19(4):991. 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) (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.

Keywords: graft rejection; ischemic type biliary lesions; orthopic liver transplantation; sphingolipids.

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Hepatocellular / blood
  • Carcinoma, Hepatocellular / chemistry
  • Carcinoma, Hepatocellular / therapy
  • Ceramides / blood*
  • Cross-Sectional Studies
  • Female
  • Graft Rejection / blood
  • Graft Rejection / diagnosis*
  • Humans
  • Liver / physiopathology*
  • Liver Neoplasms / blood
  • Liver Neoplasms / chemistry
  • Liver Neoplasms / therapy
  • Liver Transplantation
  • Male
  • Middle Aged
  • Prospective Studies
  • Tacrolimus / therapeutic use
  • Young Adult


  • Ceramides
  • Tacrolimus