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World J Gastrointest Surg. Sep 27, 2021; 13(9): 953-966
Published online Sep 27, 2021. doi: 10.4240/wjgs.v13.i9.953
Trends of rapamycin in survival benefits of liver transplantation for hepatocellular carcinoma
Yang Zhao, Yu Liu, Lin Zhou, Guo-Sheng Du, Qiang He
Yang Zhao, Yu Liu, Lin Zhou, Qiang He, Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
Guo-Sheng Du, Department of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital, Beijing 100853, China
Author contributions: Zhao Y performed the review of the literature and wrote the original draft; Liu Y, Zhou L, He Q, and Du GS reviewed and edited the manuscript; all authors read, revised, and approved the final manuscript.
Conflict-of-interest statement: The authors declare no conflict of interests for this article.
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: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Guo-Sheng Du, MD, Professor, Department of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing 100853, China. duguosheng309@126.com
Received: February 21, 2021
Peer-review started: February 21, 2021
First decision: May 8, 2021
Revised: May 17, 2021
Accepted: July 26, 2021
Article in press: July 26, 2021
Published online: September 27, 2021
Abstract

The proportion of liver transplantation (LT) for hepatocellular carcinoma (HCC) has kept on increasing over the past years and account for 20%-40% of all LT. Post-transplant HCC recurrence is considered the most important factor affecting the long-term survival of patients. The use of different types of immunosuppressive agents after LT is closely associated with an increased risk for HCC recurrence. The most commonly used conventional immunosuppressive drugs include the calcineurin inhibitors tacrolimus (FK506) and mammalian target of rapamycin inhibitor rapamycin (RAPA). Compared with tacrolimus, RAPA may carry an advantage in survival benefit because of its anti-tumor effects. However, no sufficient evidence to date has proven that RAPA could increase long-term recurrence-free survival and its anti-tumor mechanism of combined therapy remains incompletely clear. In this review, we will focus on recent advances in clinical application experience and basic research results of RAPA in patients undergoing LT for HCC to further guide the clinical practice.

Keywords: Rapamycin, Hepatocellular carcinoma, Liver transplantation, Lenvatinib, Programmed death protein-1, Huaier granule

Core Tip: Although liver transplantation (LT) is the radical method for patients with hepatocellular carcinoma (HCC), especially advanced HCC, by improving the survival benefits, the postoperative tumor recurrence seriously affects the survival of the graft and patients. The rapamycin (RAPA)-based immunosuppressive regimen has been recommended as a priority after LT due to its favorable survival benefits. In this paper, we describe the immune regulation and anti-tumor mechanism of RAPA, summarize the progress of RAPA transformation therapy after LT for HCC, further analyze the survival benefits of combined anticancer drugs and targeted drugs, and comb the prospect of immune checkpoint therapy such as programmed cell death protein 1, in order to provide a theoretical basis for RAPA transformation therapy after LT for HCC.