Circulating sterols as predictors of early allograft dysfunction and clinical outcome in patients undergoing liver transplantation

Abstract

IntroductionSensitive 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.ObjectivesHere, 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.MethodsThe 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.ResultsThe 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.ConclusionLow ratios of circulating esterified sterols are associated with a high risk of EAD and impaired clinical outcome in the early postoperative phase following LTX.Electronic supplementary materialThe online version of this article (doi:10.1007/s11306-016-1129-z) contains supplementary material, which is available to authorized users.

Fecal Metabolomics Reveals Distinct Profiles of Kidney Transplant Recipients and Healthy Controls

“…Herein, we found a decreased level of some fecal sterols, including campestanol, β-sitosterol, and stigmasterol. Although campestanol was not described within kidney dysfunction, low ratios of circulating β-sitosterol and stigmasterol were found by Ceglarek and co-workers [28] in line with our results. We suggest that this alteration might be associated with a high risk of allograft dysfunction and impaired clinical outcome following kidney transplantation.…”

A Lipidomics Study Reveals Lipid Signatures Associated with Early Allograft Dysfunction in Living Donor Liver Transplantation

“…In connection with early allograft dysfunction and primary non-function, DCD grafts appeared to show higher concentrations of lysophosphatidylcholines (lysoPCs) and increased levels of circulatory tryptophan and kynurenine at the pre-transplant stage but lower concentrations of lysoPCs at the post-transplant stage [13,14]. Ceglarek et al [15] have also demonstrated that low esterification of plant sterols in recipients after deceased donor liver transplantation was associated with a high risk of EAD. We therefore hypothesized that the recovery of liver function after liver transplantation may be linked to a disturbance in the lipid homeostasis, and in this study, we examine the lipidomic profiles in association with the development of EAD in recipients of LDLT.…”