Systematic Reviews
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Apr 27, 2024; 16(4): 650-660
Published online Apr 27, 2024. doi: 10.4254/wjh.v16.i4.650
Relative carcinogenicity of tacrolimus vs mycophenolate after solid organ transplantation and its implications for liver transplant care
Dorothy Liu, Mark M Youssef, Josephine A Grace, Marie Sinclair
Dorothy Liu, Josephine A Grace, Marie Sinclair, Department of Gastroenterology, Austin Health, Melbourne 3084, Victoria, Australia
Dorothy Liu, Marie Sinclair, Victorian Liver Transplant Unit, Austin Health, Melbourne 3084, Victoria, Australia
Dorothy Liu, Mark M Youssef, Josephine A Grace, Marie Sinclair, Department of Medicine, University of Melbourne, Melbourne 3084, Victoria, Australia
Author contributions: Liu D was involved in data interpretation, drafting of the original and revised manuscripts, and prepared some of the figures and tables; Youssef MM performed data acquisition and prepared some of the figures and tables; Sinclair M was responsible for the study design; Grace JA and Sinclair M were involved in data interpretation and critical revision of the manuscript; and all authors have read and approved the final manuscript.
Conflict-of-interest statement: The authors have no conflicts of interest to report.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
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: Dorothy Liu, B-BMed, MD, FRACP, Doctor, Department of Gastroenterology, Austin Health, 145 Studley Road, Heidelberg, Melbourne 3084, Victoria, Australia. dorothy.liu2@austin.org.au
Received: December 16, 2023
Peer-review started: December 16, 2023
First decision: January 17, 2024
Revised: January 30, 2024
Accepted: March 19, 2024
Article in press: March 19, 2024
Published online: April 27, 2024
Processing time: 130 Days and 5.5 Hours
Abstract
BACKGROUND

De novo malignancy is a leading cause of late morbidity and mortality in liver transplant recipients. Cumulative immunosuppression has been shown to contribute to post-transplant malignancy (PTM) risk. There is emerging evidence on the differential carcinogenic risk profile of individual immunosuppressive drugs, independent of the net effect of immunosuppression. Calcineurin inhibitors such as tacrolimus may promote tumourigenesis, whereas mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil, may limit tumour progression. Liver transplantation (LT) is relatively unique among solid organ transplantation in that immunosuppression monotherapy with either tacrolimus or MPA is often achievable, which makes careful consideration of the risk-benefit profile of these immunosuppression agents particularly relevant for this cohort. However, there is limited clinical data on this subject in both LT and other solid organ transplant recipients.

AIM

To investigate the relative carcinogenicity of tacrolimus and MPA in solid organ transplantation.

METHODS

A literature search was conducted using MEDLINE and Embase databases using the key terms “solid organ transplantation”, “tacrolimus”, “mycophenolic acid”, and “carcinogenicity”, in order to identify relevant articles published in English between 1st January 2002 to 11th August 2022. Related terms, synonyms and explosion of MeSH terms, Boolean operators and truncations were also utilised in the search. Reference lists of retrieved articles were also reviewed to identify any additional articles. Excluding duplicates, abstracts from 1230 records were screened by a single reviewer, whereby 31 records were reviewed in detail. Full-text articles were assessed for eligibility based on pre-specified inclusion and exclusion criteria.

RESULTS

A total of 6 studies were included in this review. All studies were large population registries or cohort studies, which varied in transplant era, type of organ transplanted and immunosuppression protocol used. Overall, there was no clear difference demonstrated between tacrolimus and MPA in de novo PTM risk following solid organ transplantation. Furthermore, no study provided a direct comparison of carcinogenic risk between tacrolimus and MPA monotherapy in solid organ transplantation recipients.

CONCLUSION

The contrasting carcinogenic risk profiles of tacrolimus and MPA demonstrated in previous experimental studies, and its application in solid organ transplantation, is yet to be confirmed in clinical studies. Thus, the optimal choice of immunosuppression drug to use as maintenance monotherapy in LT recipients is not supported by a strong evidence base and remains unclear.

Keywords: Immunosuppression; Solid organ transplantation; Liver transplantation; Carcinogenicity; Tacrolimus; Mycophenolate

Core Tip: Cumulative immunosuppression exposure is an important risk factor for the development of post-transplant malignancy. There is emerging evidence on the differential carcinogenic risk profile of individual immunosuppressive drugs, independent of the net immunosuppression effect. This review demonstrates that the evidence on the relative carcinogenicity of tacrolimus and mycophenolic acid, the two agents most commonly used as maintenance monotherapy in liver transplant patients, remains unclear. Further studies are required to determine the clinical relevance of previous experimental findings to enable physicians to tailor immunosuppression regimens to minimize individual malignancy risk in solid organ transplantation.