Published online May 21, 2020. doi: 10.3748/wjg.v26.i19.2374
Peer-review started: December 30, 2019
First decision: March 26, 2020
Revised: April 8, 2020
Accepted: April 24, 2020
Article in press: April 24, 2020
Published online: May 21, 2020
Post-transplant dyslipidemia (PTDL) is a common complication in liver recipients and closely associated with organ allograft rejection, cardiovascular events, and graft dysfunction, which subsequently lead to decreased patient survival. The crosstalk between metabolic inflammation and dyslipidemia has been recently revealed.
The role of grafts’ and recipients’ metabolic status in the development of PTDL has not been evaluated.
The present study aimed to investigate the association of pre-transplant metabolite and cytokine profiles with PTDL and establish a predictive model using clinical parameters and metabolic inflammation compounds.
A total of 396 adult patients who received primary liver transplantation between 2015 and 2017 were enrolled. Metabolomics and cytokines were analyzed using recipients’ pre-transplant peripheral blood in a training set (n = 72). In addition, an integrated prediction model was established according to the clinical risk factors and metabolic inflammation compounds and further verified in a validation set (n = 144).
A 3-month remodeling of lipid homeostasis after liver transplantation was found in liver recipients. There were 278 (70.2%) patients who developed PTDL during a follow-up period of 1.78 (1.00, 2.97) years. The PTDL group showed a significantly lower tumor-free survival and overall survival than the non-PTDL group in patients with hepatocellular carcinoma (n = 169). In addition, the metabolomic analysis showed that metabolic features discriminating between the PTDL and non-PTDL groups were associated with lipid and glucose metabolism-associated pathways. Among metabolites and cytokines differentially expressed between the two groups, interleukin (IL)-12 (p70) showed the best diagnostic accuracy and significantly increased the predictive value when it was incorporated into the clinical model in both training and validation sets.
PTDL is very common in liver recipients and associated with a poor prognosis. Among the metabolic inflammation compounds, IL-12 (p70) could be a valid predictor of PTDL and remarkably improve the predictive ability of the clinical model.
Recipients’ pre-transplant serum IL-12 (p70) level is associated with the risk of PTDL and has potential clinical value for predicting PTDL. We recommend prophylactic regulation of metabolic inflammation for the prevention of the development of PTDL in liver transplantation candidates.