Metabolomic profiling of liver tumors and its impact on liver regeneration

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Postoperative liver dysfunction (LD) still represents a severe complication in patients undergoing liver resection and its incidence is estimated at 10–20%. As postoperative LD commonly develops as a result of delayed liver regeneration, it is most relevant to reach a comprising understanding of this process. Thus, we aimed to investigate the perioperative dynamic of circulating metabolites, as well as differences in the metabolic profile of patients with and without postoperative LD using an unbiased metabolomics approach. Plasma from 95 prospectively included patients was collected preoperatively and on the first and fifth postoperative day (POD5). Per patient and time point 180 metabolites were assessed using the Biocrates p180-kit. Development of LD was prospectively recorded. 21 patients (19.95%) suffered from postoperative LD. We observed significant dynamics in the metabolic profile after liver surgery, that tended to normalize upon POD5. Further, we were able to document differences in the concentration of 120 metabolites between patients with and without postoperative LD. Interestingly, the family of sphingolipids showed an evident accumulation of differentially abundant metabolites in patients with LD at several time points, while the total amount of sphingolipids did not differ. Within this study we present the first data on the metabolic profile in patients undergoing liver resection and in patients with delayed liver regeneration. While we found a plethora of potential markers for postoperative LD at various time points, we also present hypothesis generating data and the opportunity to characterize potentially targetable pathways for improvement of postoperative liver regeneration.