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

Introduction: 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.

Objectives: 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.

Conclusion: 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.