Case Control Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Dec 16, 2021; 9(35): 10792-10804
Published online Dec 16, 2021. doi: 10.12998/wjcc.v9.i35.10792
Impact of cytomegalovirus infection on biliary disease after liver transplantation - maybe an essential factor
Jing-Yi Liu, Jian-Rui Zhang, Li-Ying Sun, Zhi-Jun Zhu, Lin Wei, Wei Qu, Zhi-Gui Zeng, Ying Liu, Xin-Yan Zhao
Jing-Yi Liu, Jian-Rui Zhang, Li-Ying Sun, Zhi-Jun Zhu, Lin Wei, Wei Qu, Zhi-Gui Zeng, Ying Liu, Xin-Yan Zhao, Liver Transplantation Center, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
Jing-Yi Liu, Jian-Rui Zhang, Li-Ying Sun, Zhi-Jun Zhu, Lin Wei, Wei Qu, Zhi-Gui Zeng, Ying Liu, Clinical Center for Pediatric Liver Transplantation, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
Jing-Yi Liu, Jian-Rui Zhang, Li-Ying Sun, Zhi-Jun Zhu, Lin Wei, Wei Qu, Zhi-Gui Zeng, Ying Liu, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
Li-Ying Sun, Intensive Care Unit, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
Author contributions: Sun LY, Zhang JR, and Liu JY participated in the research design; Zhang JR and Liu JY participated in sample collection, data analysis, and manuscript writing and contributed equally to this work; Zhu ZJ, Wei L, Qu W, Liu Y, Zeng ZG, and Zhao XY participated in performing the research; All authors have read and approve the final manuscript.
Supported by The National Natural Science Foundation of China, No. 81570586.
Institutional review board statement: The study was reviewed and approved by the Capital Medical University affiliated Beijing Friendship Hospital Institutional Review Board.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors declare no conflicts of interest.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
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: Li-Ying Sun, MD, PhD, Chief Doctor, Professor, Liver Transplantation Center, Beijing Friendship Hospital, Capital Medical University, No. 95 Yongan Road, Beijing 100050, China. sunxlx@outlook.com
Received: May 13, 2021
Peer-review started: May 13, 2021
First decision: July 4, 2021
Revised: July 17, 2021
Accepted: September 14, 2021
Article in press: September 14, 2021
Published online: December 16, 2021
Processing time: 210 Days and 21.1 Hours
Abstract
BACKGROUND

Cytomegalovirus (CMV) infection is common in liver transplant (LT)_ recipients, and biliary complications occur in a large number of patients. It has been reported that CMV-DNA is more detectable in bile than in blood.

AIM

To investigate the effects of CMV infection on biliary complications by comparing the levels of CMV-DNA in the bile and blood of patients after LT.

METHODS

We conducted a retrospective analysis of 57 patients who underwent LT, 10 of these patients had no biliary complications and 47 patients had biliary complications. We also compared the levels of CMV-DNA in patients’ bile and blood, which were sampled concurrently. We used RNAscope technology to identify CMV in paraffin-embedded liver sections.

RESULTS

CMV-DNA was not detected in bile samples and was detected in 2 blood samples from patients without biliary complications. In the 47 patients with biliary complications, CMV-DNA was detected in 22 bile samples and 8 blood samples, both bile and blood samples were positive for CMV-DNA in 6 patients. The identification rate of CMV-DNA in blood was 17.0%, and was 46.8% in bile. Moreover, tissue samples from 4 patients with biliary complications tested positive using RNAscope technology but were negative with hematoxylin and eosin staining. During the follow-up period, graft failure occurred in 13 patients with biliary complications, 8 of whom underwent retransplantation, and 3 died. CMV-DNA in bile was detected in 9 of 13 patients with graft failure.

CONCLUSION

In patients with biliary complications, the identification rate of CMV-DNA in bile was higher than that in blood. Blood CMV-DNA negative patients with biliary complications should still be monitored for CMV-related biliary tract diseases. Potential occult CMV infection may also be a contributing etiological factor in the development of graft failure.

Keywords: Liver transplantation, Cytomegalovirus infection, Graft failure, Biliary complications, RNAscope in situ hybridization, Retrospective study

Core Tip: For patients with biliary complications after liver transplantation, the clinical doctors should be alert to cytomegalovirus (CMV)-related biliary tract diseases even though the test of CMV-DNA in the blood is negative. The test for CMV-DNA in bile may be a novel approach for diagnosing occult CMV-related biliary disease. There has been no study on diagnosing CMV-related biliary complications after liver transplant by detecting CMV-DNA in isolated bile. Occult CMV infection in the biliary tract may be associated with biliary stenosis and a contributing factor to graft failure, leading to high mortality after surgery.