Retrospective Cohort Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 7, 2019; 25(37): 5630-5640
Published online Oct 7, 2019. doi: 10.3748/wjg.v25.i37.5630
Post-transplant infection improves outcome of hepatocellular carcinoma patients after orthotopic liver transplantation
Jia-Shuo Chao, Sen-Lin Zhao, Si-Wen Ou-yang, Yong-Bing Qian, Ai-Qun Liu, Hua-Mei Tang, Lin Zhong, Zhi-Hai Peng, Jun-Ming Xu, Hong-Cheng Sun
Jia-Shuo Chao, Si-Wen Ou-yang, Lin Zhong, Zhi-Hai Peng, Jun-Ming Xu, Hong-Cheng Sun, Department of General Surgery, Shanghai Organ Transplantat Medical Center, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 200080, China
Sen-Lin Zhao, Department of Colorectal Surgery, Fudan University, Shanghai Cancer Center, Shanghai 200032, China
Yong-Bing Qian, Division of Critical Care, Department of Liver Surgery, Renji Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 200127, China
Ai-Qun Liu, Department of Radiology, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 200080, China
Hua-Mei Tang, Department of Pathology, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 200080, China
Author contributions: Zhao SL and Chao JS collected and analyzed the data, and drafted the manuscript; Ou-yang SW followed the patients and collected the data; Qian YB contributed to PTI identification and diagnosis of HCC recurrence; Liu AQ assisted in identification of PTI and HCC recurrence from radiologic perspective; Tang HM performed the histological examination of the explant livers, and provided pathological diagnosis and staging of the tumors; Zhong L, Peng ZH, and Xu JM performed liver transplantation and followed the patients; Sun HC performed liver transplantation, acquired the funding, revised the manuscript, and supervised the research group.
Supported by the National Natural Science Foundation of China, No. 81672846 and No. 81670595.
Institutional review board statement: This study was reviewed and approved by the Institution Review Board of Shanghai General Hospital, Shanghai Jiaotong University.
Informed consent statement: Written informed consent was obtained from all patients or their legal guardians for being included in the study.
Conflict-of-interest statement: The authors declare that they have no competing interests.
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: Hong-Cheng Sun, MD, PhD, Associate Chief Physician, Associate Professor, Vice Director, Surgeon, Surgical Oncologist, Department of General Surgery, Shanghai Organ Transplantation Medical Center, Shanghai General Hospital, 100 Haining Road, Shanghai 200080, China. sunhongchengmd@163.com
Telephone: +86-21-632400903131 Fax: +86-21-55900622
Received: June 15, 2019
Peer-review started: June 17, 2019
First decision: July 21, 2019
Revised: August 22, 2019
Accepted: September 9, 2019
Article in press: September 9, 2019
Published online: October 7, 2019
Processing time: 108 Days and 11 Hours
Abstract
BACKGROUND

Tumor recurrence after orthotopic liver transplantation (OLT) remains a serious threat for long-term survival of the recipients with hepatocellular carcinoma (HCC), since very few factors or measures have shown impact on overcoming HCC recurrence after OLT. Postoperative infection suppresses tumor recurrence and improves patient survival in lung cancer and malignant glioma probably via stimulating the immune system. Post-transplant infection (PTI), a common complication, is deemed to be harmful for the liver transplant recipients from a short-term perspective. Nevertheless, whether PTI inhibits HCC recurrence after OLT and prolongs the long-term survival of HCC patients needs to be clarified.

AIM

To investigate the potential influence of PTI on the survival and tumor recurrence of patients with HCC after OLT.

METHODS

A total of 238 patients with HCC who underwent OLT between August 2002 and July 2016 at our center were retrospectively included and accordingly subdivided into a PTI group (53 patients) and a non-PTI group (185 patients). Univariate analyses, including the differences of overall survival (OS), recurrence-free survival (RFS), and post-recurrence survival (PRS), between the PTI and non-PTI subgroups as well as survival curve analysis were performed by the Kaplan-Meier method, and the differences were compared using the log rank test. The variables with a P-value < 0.1 in univariate analyses were included in the multivariate survival analysis by using a Cox proportional-hazards model.

RESULTS

The 1-, 3-, and 5-year OS and RFS rates of the whole cohort were 86.6%, 69.0%, and 63.6%, and 75.7%, 60.0%, and 57.3%, respectively. The 1-, 3-, and 5-year OS rates for the PTI patient group (96.0%, 89.3%, and 74.0%) were significantly higher than those for the non-PTI group (84.0%, 63.4%, and 60.2%) (P = 0.033). The absence of PTI was an independent risk factor for dismal OS (relative risk [RR] = 2.584, 95%CI: 1.226-5.449) and unfavorable RFS (RR = 2.683, 95%CI: 1.335-5.390). Subgroup analyses revealed that PTI remarkably improved OS (P = 0.003) and RFS (P = 0.003) rates of HCC patients with vascular invasion (IV), but did not impact on OS (P = 0.404) and RFS (P = 0.304) of patients without VI. Among the patients who suffered post-transplant tumor recurrence, patients with PTI showed significantly better OS (P = 0.026) and PRS (P = 0.042) rates than those without PTI.

CONCLUSION

PTI improves OS and RFS of the transplant HCC patients at a high risk for post-transplant death and tumor recurrence, which is attributed to suppressive effect of PTI on HCC recurrence.

Keywords: Liver transplantation; Liver cancer; Infection; Survival; Tumor recurrence

Core tip: Post-transplant infection (PTI) is routinely deemed as a harmful event for liver transplant recipients from a short-term perspective. Nevertheless, the present study demonstrated that PTI prolonged overall and recurrence-free survival of the patients with hepatocellular carcinoma (HCC) at a high risk for post-transplant death and tumor recurrence, which may be attributed to the persistent tumor suppressive effect of PTI on HCC recurrence after orthotopic liver transplantation (OLT). Further prospective multicenter investigations and experimental studies regarding the mechanism by which PTI inhibits HCC progression may contribute to future successful prophylaxis of HCC recurrence after OLT.