Systematic Reviews
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 21, 2019; 25(35): 5356-5375
Published online Sep 21, 2019. doi: 10.3748/wjg.v25.i35.5356
De novo malignancies after liver transplantation: The effect of immunosuppression-personal data and review of literature
Tommaso Maria Manzia, Roberta Angelico, Carlo Gazia, Ilaria Lenci, Martina Milana, Oludamilola T Ademoyero, Domiziana Pedini, Luca Toti, Marco Spada, Giuseppe Tisone, Leonardo Baiocchi
Tommaso Maria Manzia, Carlo Gazia, Luca Toti, Giuseppe Tisone, HPB and Transplant Unit, Department of Surgery, University of Rome Tor Vergata, Rome 00133, Italy
Roberta Angelico, Domiziana Pedini, Marco Spada, Division of Abdominal Transplantation and HPB Surgery, Bambino Gesù Children's Hospital IRCCS, Rome 00165, Italy
Carlo Gazia, Oludamilola T Ademoyero, Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC 27101, United States
Ilaria Lenci, Martina Milana, Leonardo Baiocchi, Hepatology and Liver Transplant Unit, University of Tor Vergata, Rome 00133, Italy
Author contributions: Manzia TM and Angelico R contributed equally to the work, paper conception and design and critical revision; Gazia C, Lenci I, Milana M, Ademoyero OT, Pedini D and Toti L contributed to acquisition of data, analysis and interpretation, drafting of manuscript and critical revision; Spada M, Tisone G and Baiocchi L contributed to study conception and critical revision.
Conflict-of-interest statement: The authors declare they have no conflicts of interest to disclose.
PRISMA 2009 Checklist statement: Authors read the PRISMA 2009 Checklist and the manuscript was prepared and revised according to the PRISMA 2009.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Tommaso Maria Manzia, MD, PhD, Assistant Professor, HPB and Transplant Unit, Department of Surgery, University of Rome Tor Vergata, Viale Oxford, 81, Rome 00133, Italy. tomanzia@libero.it
Telephone: +39-6-20902498
Received: May 2, 2019
Peer-review started: May 4, 2019
First decision: May 30, 2019
Revised: August 8, 2019
Accepted: August 24, 2019
Article in press: August 24, 2019
Published online: September 21, 2019
Abstract
BACKGROUND

Immunosuppression has undoubtedly raised the overall positive outcomes in the post-operative management of solid organ transplantation. However, long-term exposure to immunosuppression is associated with critical systemic morbidities. De novo malignancies following orthotopic liver transplants (OLTs) are a serious threat in pediatric and adult transplant individuals. Data from different experiences were reported and compared to assess the connection between immunosuppression and de novo malignancies in liver transplant patients.

AIM

To study the role of immunosuppression on the incidence of de novo malignancies in liver transplant recipients.

METHODS

A systematic literature examination about de novo malignancies and immunosuppression weaning in adult and pediatric OLT recipients was described in the present review. Worldwide data were collected from highly qualified institutions performing OLTs. Patient follow-up, immunosuppression discontinuation and incidence of de novo malignancies were reported. Likewise, the review assesses the differences in adult and pediatric recipients by describing the adopted immunosuppression regimens and the different type of diagnosed solid and blood malignancy.

RESULTS

Emerging evidence suggests that the liver is an immunologically privileged organ able to support immunosuppression discontinuation in carefully selected recipients. Malignancies are often detected in liver transplant patients undergoing daily immunosuppression regimens. Post-transplant lymphoproliferative diseases and skin tumors are the most detected de novo malignancies in the pediatric and adult OLT population, respectively. To date, immunosuppression withdrawal has been achieved in up to 40% and 60% of well-selected adult and pediatric recipients, respectively. In both populations, a clear benefit of immunosuppression weaning protocols on de novo malignancies is difficult to ascertain because data have not been specified in most of the clinical experiences.

CONCLUSION

The selected populations of tolerant pediatric and adult liver transplant recipients greatly benefit from immunosuppression weaning. There is still no strong clinical evidence on the usefulness of immunosuppression withdrawal in OLT recipients on malignancies. An interesting focus is represented by the complete reconstitution of the immunological pathways that could help in decreasing the incidence of de novo malignancies and may also help in treating liver transplant patients suffering from cancer.

Keywords: Pediatric liver transplant, Immunosuppression weaning, Clinical operational tolerance, Adult liver transplant, Graft rejection, Immune system, De novo malignancies, Immunosuppression minimization, Cancer

Core tip: A systematic literature examination about de novo malignancies and immunosuppression weaning both in adult and pediatric orthotopic liver transplant recipients was described in the present review. Even though conclusive evidence on immunosuppression withdrawal in orthotopic liver transplant recipients with regard to malignancies are lacking, we can argue that the reconstitution of the immunological pathway could decrease the incidence of de novo malignancies and may also help in treating liver transplant patients suffering from cancers.