Clinical And Translational Research
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 21, 2020; 26(19): 2374-2387
Published online May 21, 2020. doi: 10.3748/wjg.v26.i19.2374
Predicting dyslipidemia after liver transplantation: A significant role of recipient metabolic inflammation profile
Hai-Tao Huang, Xue-You Zhang, Cheng Zhang, Qi Ling, Shu-Sen Zheng
Hai-Tao Huang, Xue-You Zhang, Cheng Zhang, Qi Ling, Shu-Sen Zheng, Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
Qi Ling, Shu-Sen Zheng, Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, Zhejiang Province, China
Author contributions: Ling Q designed the research; Huang HT, Zhang XY, and Zhang C performed the research and analyzed the data; Huang HT wrote the manuscript; Zheng SS and Ling Q reviewed the manuscript; all authors approved the final version of the article.
Supported by the National Natural Science Foundation of China, No. 81771713; Zhejiang Provincial Natural Science Foundation of China, No. LR18H030001.
Institutional review board statement: The study was reviewed and approved by the First Affiliated Hospital, Zhejiang University School of Medicine Institutional Review Board.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors declare that there is no conflict of interest to be disclosed.
Data sharing statement: The original anonymous dataset is available on request from the corresponding author at
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Qi Ling, MD, PhD, Doctor, Surgeon, Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, No. 79, Qingchun Road, Hangzhou 310003, Zhejiang Province, China.
Received: December 30, 2019
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
Research background

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.

Research motivation

The role of grafts’ and recipients’ metabolic status in the development of PTDL has not been evaluated.

Research objectives

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.

Research methods

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).

Research results

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.

Research conclusions

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.

Research perspectives

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.