Retrospective Cohort Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Surg. Dec 27, 2023; 15(12): 2727-2738
Published online Dec 27, 2023. doi: 10.4240/wjgs.v15.i12.2727
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
Processing time: 106 Days and 22.5 Hours
Abstract
BACKGROUND

Clinical factors predicting graft survival (GS) after ABO-incompatible (ABOi) liver transplantation (LT), and differences between recipients with and without hepatocellular carcinoma (HCC) are unclear.

AIM

To analyze the impact of serial serum tacrolimus trough concentration in recipients with or without HCC) in ABOi living-donor liver transplantation (LDLT).

METHODS

We analyzed a historical cohort of 89 recipients who underwent ABOi LDLT, including 47 patients with HCC.

RESULTS

The 1-, 3-, 5-, and 10-year GS rates were 85.9%, 73.3%, 71.4%, and 71.4%, respectively, and there were no significant differences between HCC and non-HCC recipients. In multivariate Cox-regression analyses, tacrolimus trough concentrations below 5.4 ng/mL at 24 wk post-LT, in addition to the antibody-mediated rejection (AMR) were associated with poor-graft outcomes. In HCC patients, AMR [hazard ratio (HR) = 63.20, P < 0.01] and HCC recurrence (HR = 20.72, P = 0.01) were significantly associated with poor graft outcomes. HCCs outside Milan criteria, and tacrolimus concentrations at 4 wk post-LT > 7.3 ng/mL were significant predictive factors for HCC recurrence. After propensity score matching, patients with high tacrolimus concentrations at 4 wk had significantly poor recurrence-free survival.

CONCLUSION

Elevated tacrolimus levels at 4 wk after ABOi LDLT have been found to correlate with HCC recurrence. Therefore, careful monitoring and control of tacrolimus levels are imperative in ABOi LT recipients with HCC.

Keywords: ABO-incompatible; Liver transplantation; Tacrolimus; Hepatocellular carcinoma

Core Tip: Maintenance immunosuppression with calcineurin inhibitors (CNIs) such as tacrolimus or cyclosporine is the current standard regimen for liver transplantation (LT) patients, and this might be important in the preventing antibody-mediated rejection in ABO-incompatible (ABOi) LT. However, increased exposure to CNIs, especially in the first month after LT, is reported to be a risk factor for HCC recurrence. Nevertheless, the appropriate adjustment of immunosuppressant doses in ABOi LT recipients with and without HCC has not yet been determined. In this study, greater early exposure to tacrolimus was associated with HCC recurrence, whereas lesser exposures at later time points was associated with poorer long-term graft outcomes, suggesting that adjustment of serum tacrolimus concentration according to the presence of HCC may be required to improve graft outcomes.