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.
Highlights
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
No or only low disturbances post-LTX were seen in circulating amino acids as well as acylcarnitines
Circulating sterols are composed of cholesterol, an essential component of membranes by regulating the fluidity of the bilayer, several precursors of cholesterol as lanosterol which are markers for cholesterol synthesis, and plant sterols which are exclusively derived from dietary sources (Kuksis 2001)
Summary
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. Sensitive and specific assessment of the hepatic metabolism after LTX remains essential for early detection of postoperative dysfunction and consecutive adjustment of the therapeutic regime. A model for the quantitative assessment of EAD after LTX has been validated (model for early allograft function scoring, MEAF) (Pareja et al 2015) This score, based on the parameters ALT, bilirubin and INR calculated at day 3 post-LTX, provides improved graft function assessment than the single parameters (Pareja et al 2015) while at the same time being a predictor of both recipient and graft survival. Evaluation of the actual parenchymal function and precise distinction between a toxic and hypoxic liver injury can be challenging (Hickman et al 1997; Shaked et al 1997; Tanaka et al 2000; Sear 2002) since routine parameters may rather reflect pre- and perioperative liver cell injury due to ischemia and organ preservation than the residual metabolic capacity of the transplanted liver
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