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©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
Association between the early high level of serum tacrolimus and recurrence of hepatocellular carcinoma in ABO-incompatible liver transplantation
Ji Won Han, Jong Young Choi, Eun Sun Jung, Ji Hoon Kim, Hee Sun Cho, Jae-Sung Yoo, Pil Soo Sung, Jeong Won Jang, Seung Kew Yoon, Ho Joong Choi, Young Kyoung You
Ji Won Han, Jong Young Choi, Ji Hoon Kim, Hee Sun Cho, Jae-Sung Yoo, Pil Soo Sung, Jeong Won Jang, Seung Kew Yoon, Department of Internal Medicine, The Catholic University of Korea, Seoul 06591, South Korea
Ji Won Han, Jong Young Choi, Ji Hoon Kim, Hee Sun Cho, Jae-Sung Yoo, Pil Soo Sung, Jeong Won Jang, Seung Kew Yoon, The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea
Eun Sun Jung, Department of Hospital Pathology, The Catholic University of Korea, Seoul 06591, South Korea
Ho Joong Choi, Young Kyoung You, Department of Surgery, The Catholic University of Korea, Seoul 06591, South Korea
Co-corresponding authors: Eun Sun Jung and Jong Young Choi.
Author contributions: Choi JY designed the study. Choi JY, Sung PS, Jang JW, Yoon SK, Kim JH, Cho HS, Yoo JS, Choi HJ, Jung ES and You YK provided clinical data. Han JW, Jung ES and Choi JY collected and analyzed the data. Jung ES and Choi JY supervised the analyses and the manuscript. Han JW, Jung ES, and Choi JY wrote and edited the manuscript. Jung ES and Choi JY contributed equally to this work as co-corresponding authors. The reasons for designating Jung ES and Choi JY as co-corresponding authors are threefold. First, the research was performed as a collaborative effort, and the designation of co-corresponding authorship accurately reflects the distribution of responsibilities and burdens associated with the time and effort required to complete the study and the resultant paper. This also ensures effective communication and management of post-submission matters, ultimately enhancing the paper's quality and reliability. Second, the overall research team encompassed authors with a variety of expertise and skills from different fields, and the designation of co-corresponding authors best reflects this diversity. This also promotes the most comprehensive and in-depth examination of the research topic, ultimately enriching readers' understanding by offering various expert perspectives. Third, Jung ES and Choi JY contributed efforts of equal substance throughout the research process. The choice of these researchers as co-corresponding authors acknowledges and respects this equal contribution, while recognizing the spirit of teamwork and collaboration of this study. In summary, we believe that designating Jung ES and Choi JY as co-corresponding authors of is fitting for our manuscript as it accurately reflects our team's collaborative spirit, equal contributions, and diversity.
Supported by National Research Foundation of Korea, NO. 2022R1I1A1A0106363612; Korea Health Industry Development Institute, No. HI23C1489.
Institutional review board statement: This study was approved by the Institutional Review Board of Seoul St. Mary’s Hospital (approval number: KC22RISI0921) and was performed according to the Declaration of Helsinki.
Conflict-of-interest statement: All the Authors have no conflict of interest related to the manuscript.
Data sharing statement: The data used to conduct the research are available from the corresponding author upon request.
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:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Jong Young Choi, MD, PhD, Professor, Department of Internal Medicine, The Catholic University of Korea, No. 222 Banpodaero, Seoul 06591, South Korea. jychoi@catholic.ac.kr
Received: September 11, 2023
Peer-review started: September 11, 2023
First decision: October 9, 2023
Revised: October 18, 2023
Accepted: December 1, 2023
Article in press: December 1, 2023
Published online: December 27, 2023
ARTICLE HIGHLIGHTS
Research background
ABO-incompatible (ABOi) liver transplantation (LT) has posed significant challenges due to its impact on graft survival and the occurrence of complications like antibody-mediated rejection (AMR). The outcomes of ABOi living-donor LT (LDLT) have shown considerable variability in previous studies. This research aimed to investigate the long-term outcomes of ABOi LDLT and associated risk factors.
Research motivation
Understanding the factors that influence graft survival (GS) and complications in ABOi LDLT recipients is essential for improving the clinical outcomes. Identifying the impact of tacrolimus concentration on graft outcomes, especially in patients with or without hepatocellular carcinoma (HCC), can provide valuable insights for optimizing immunosuppressive therapy.
Research objectives
The primary objectives of this study were to assess the long-term graft outcomes in ABOi LDLT and analyze the associated risk factors. Subgroup analyses were performed to evaluate GS and risk factors based on the presence or absence of HCC. Additionally, the study aimed to investigate the influence of serial serum tacrolimus trough concentration on graft outcomes in both HCC and non-HCC recipients.
Research methods
A retrospective analysis was conducted on a cohort of 89 ABOi LDLT recipients. Various clinical, laboratory, and radiological data were collected for each patient. Desensitization and immunosuppression protocols were followed, including the use of rituximab and tacrolimus. The impact of tacrolimus trough concentration on GS and HCC recurrence was analyzed using statistical methods.
Research results
The study found that AMR was a common risk factor affecting GS in both HCC and non-HCC ABOi LDLT recipients. Early exposure to high tacrolimus concentrations was associated with HCC recurrence, while lower concentrations at later time points were linked to poorer long-term graft outcomes in non-HCC patients. Maintaining a narrow range of tacrolimus concentrations between 5.4 and 7.3 ng/mL may be beneficial.
Research conclusions
This research highlighted the importance of monitoring and managing the calcineurin inhibitor (CNI) concentrations in ABOi LDLT recipients. The study also suggested that tailoring tacrolimus concentration based on the presence of HCC can optimize graft outcomes. Minimizing CNIs, especially in HCC patients, may reduce the risk of HCC recurrence.
Research perspectives
Future studies should validate the optimal tacrolimus concentration cutoffs and explore additional strategies to improve the outcomes of ABOi LDLT recipients. Multicenter studies considering various risk factors are warranted to develop predictive models for this patient population.
