title: Circulating sterols as predictors of early allograft dysfunction and clinical outcome in patients undergoing liver transplantation.
abstract: BACKGROUND
  Sensitive and specific assessment of the hepatic graft metabolism after liver transplantation (LTX) is essential for early detection of postoperative dysfunction implying the need for consecutive therapeutic interventions.
  
  
  OBJECTIVE
  Here, we assessed circulating liver metabolites of the cholesterol pathway, amino acids and acylcarnitines and evaluated their predictive value on early allograft dysfunction (EAD) and clinical outcome in the context of LTX.
  
  
  METHODS
  The metabolites were quantified in the plasma of 40 liver graft recipients one day pre- and 10 days post-LTX by liquid chromatography/tandem mass spectrometry (LC-MS/MS). Plant sterols as well as cholesterol and its precursors were determined in the free and esterified form; lanosterol in the free form only. Metabolites and esterification ratios were compared to the model for early allograft function scoring (MEAF) which is calculated at day 3 post-LTX from routine parameters defining EAD.
  
  
  RESULTS
  The hepatic esterification ratio of all sterols, but not amino acids and acylcarnitine concentrations, showed substantial metabolic disturbances post-LTX and correlated to the MEAF. In ROC analysis, the low esterification ratio of β-sitosterol and stigmasterol from day 1 and of the other sterols from day 3 were predictive for a high MEAF, i.e. EAD. Additionally, the ratio of esterified β-sitosterol and free lanosterol were predictive for all days and the esterification ratio of the other sterols at day 3 or 4 post-LTX for 3-month mortality.
  
  
  CONCLUSIONS
  Low ratios of circulating esterified sterols are associated with a high risk of EAD and impaired clinical outcome in the early postoperative phase following LTX.
authors.affiliation: Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, University of Leipzig, 04103 Leipzig, Germany.|LIFE-Leipzig Research Center for Civilization Diseases, University Leipzig, Philipp-Rosenthal-Strasse 27, 04103 Leipzig, Germany.
authors.forename: Uta
authors.initials: U
authors.lastname: Ceglarek
authors.affiliation: Research Laboratories and Clinic of Visceral, Transplantation, Thoracic, and Vascular Surgery, University Hospital Leipzig, University of Leipzig, Liebigstraße 19, 04103 Leipzig, Germany.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Kresse
authors.affiliation: Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, University of Leipzig, 04103 Leipzig, Germany.|LIFE-Leipzig Research Center for Civilization Diseases, University Leipzig, Philipp-Rosenthal-Strasse 27, 04103 Leipzig, Germany.
authors.forename: Susen
authors.initials: S
authors.lastname: Becker
authors.affiliation: Department of Laboratory Medicine, Institute of Clinical Chemistry, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
authors.forename: Georg Martin
authors.initials: GM
authors.lastname: Fiedler
authors.affiliation: Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, University of Leipzig, 04103 Leipzig, Germany.|LIFE-Leipzig Research Center for Civilization Diseases, University Leipzig, Philipp-Rosenthal-Strasse 27, 04103 Leipzig, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Thiery
authors.affiliation: Research Laboratories and Clinic of Visceral, Transplantation, Thoracic, and Vascular Surgery, University Hospital Leipzig, University of Leipzig, Liebigstraße 19, 04103 Leipzig, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Quante
authors.affiliation: Research Laboratories and Clinic of Visceral, Transplantation, Thoracic, and Vascular Surgery, University Hospital Leipzig, University of Leipzig, Liebigstraße 19, 04103 Leipzig, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Wieland
authors.affiliation: Research Laboratories and Clinic of Visceral, Transplantation, Thoracic, and Vascular Surgery, University Hospital Leipzig, University of Leipzig, Liebigstraße 19, 04103 Leipzig, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Bartels
authors.affiliation: Research Laboratories and Clinic of Visceral, Transplantation, Thoracic, and Vascular Surgery, University Hospital Leipzig, University of Leipzig, Liebigstraße 19, 04103 Leipzig, Germany.
authors.forename: Gabriela
authors.identifier: 0000-0002-4670-4543
authors.initials: G
authors.lastname: Aust
keywords: Liver transplantation; MEAF; Sterol metabolism