Prospective Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Pathophysiol. May 22, 2021; 12(3): 51-58
Published online May 22, 2021. doi: 10.4291/wjgp.v12.i3.51
Impact of cytomegalovirus reactivation just before liver transplantation: A prospective cohort study
Claudio Marcel B Stadnik, Cassia Ferreira B Caurio, Edison M Rodrigues-Filho, Wagner L Nedel, Guido PC Cantisani, Maria L Zanotelli, Alessandro C Pasqualotto
Claudio Marcel B Stadnik, Infection Control Department, Santa Casa de Misericordia de Porto Alegre, Porto Alegre 90075075, RS, Brazil
Cassia Ferreira B Caurio, Alessandro C Pasqualotto, Molecular Biology Laboratory, Santa Casa de Misericordia de Porto Alegre, Porto Alegre 90075075, RS, Brazil
Edison M Rodrigues-Filho, Wagner L Nedel, Intensive Care, Santa Casa de Misericordia de Porto Alegre, Porto Alegre 90075075, RS, Brazil
Guido PC Cantisani, Maria L Zanotelli, Liver Transplant Unit, Santa Casa de Misericordia de Porto Alegre, Porto Alegre 90075075, RS, Brazil
Alessandro C Pasqualotto, Infectious Diseases Unit, Universidade Federal de Ciencias da Saude de Porto Alegre, Porto Alegre 90035075, RS, Brazil
Author contributions: Stadnik CMB performed the research, collected and analyzed the data, and wrote the paper; Pasqualotto AC wrote the paper and reviewed of manuscript; Caurio CFB collected data and performed laboratory analyses; Rodrigues-Filho EM, Cantisani GP and Zanotelli ML designed the study and reviewed the manuscript; all authors have read and approved the final manuscript.
Supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)–Brazil, No. 479880/2012-3.
Institutional review board statement: This study was approved by the Research Ethics Committee at Santa Casa de Misericordia of Porto Alegre (294/2010).
Conflict-of-interest statement: The authors declare no conflict of interest.
Data sharing statement: No additional data are available.
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: Alessandro C Pasqualotto, MD, PhD, Adjunct Professor, Molecular Biology Laboratory, Santa Casa de Misericordia de Porto Alegre, Av Independência 155, Hospital Dom Vicente Scherer, heliponto, Porto Alegre 90075075, RS, Brazil. pasqualotto@ufcspa.edu.br
Received: September 23, 2020
Peer-review started: September 23, 2020
First decision: November 16, 2020
Revised: November 30, 2020
Accepted: February 25, 2021
Article in press: February 25, 2021
Published online: May 22, 2021
Processing time: 232 Days and 12 Hours
ARTICLE HIGHLIGHTS
Research background

The overall incidence of cytomegalovirus (CMV) infection is between 50%-60% in liver transplant recipients, with 20%-30% of patients demonstrating a symptomatic infection[1]. The incidence of post-transplant CMV infection depends mainly on the recipient and donor serological profile. The lowest-risk groups include positive serology for both donors and recipients (D+/R+ status) and a negative status for both donors and recipients (D-/R-). Although reactivation of CMV infection is mostly described in the context of overt immunosuppression, reactivation may also occur in critically ill immunocompetent patients[4-7] associated with increased mortality[8,9].

Research motivation

A subgroup of particular interest is patients with chronic liver diseases[10,11]. Whether CMV reactivation in these individuals that are listed for liver transplantation has any impact on post-transplant outcomes has not been determined[12].

Research objectives

To determine the incidence of reactivated CMV prior to liver transplantation.

Research methods

This was a prospective cohort study that evaluated adult (≥ 18 years of age) patients with chronic liver disease listed to undergo liver transplantation at a referral hospital for organ transplantation in Latin America. Patients were followed for a minimum of 1 year after liver transplantation. During this period, all episodes of CMV reactivation [detected by either quantitative real-time PCR (qRT-PCR) and/or pp65 antigenemia] were documented, as well as events of CMV disease, organ rejection and overall mortality. Screening for CMV reactivation was performed monthly for the first three months after transplantation or whenever the patient presented with clinical symptoms. At the time the enrolled participants were called in for liver transplantation, plasma was collected for analysis of CMV qRT-PCR.

Research results

A total of 72 patients were enrolled in the study. Four patients died before transplantation, thus 68 patients were followed up for a median of 44 mo (25%-75% percentile: 20-50 mo). CMV reactivation was demonstrated in 31.9% (23/72) of patients before transplantation. Median plasma CMV DNA concentration in these patients was 1.212 IU/mL (25%-75% percentile: 560-4.197 IU/mL). Following liver transplantation, CMV infection occurred in 16/67 patients (23.8%).

The crude mortality rate was 20/68 (29.4%), median 7.7 mo (perc 25-75: 1-12), and 7/22 (31.8%) in patients with pre-transplant CMV reactivation (P = 0.763). In Kaplan-Meier analyses, pre-transplant CMV reactivation had no impact on mortality following liver transplantation (log rank: 0.92) (Figure 1). Cox regression analysis also identified no statistically significant factor for mortality in this cohort.

Research conclusions

The findings of this study suggest that pre-transplant CMV reactivation has no influence on liver transplantation results, and has no impact on post-transplant CMV reactivation or overall mortality.

Research perspectives

Based on this study, screening for CMV DNAemia before liver transplantation does not seem justified. A larger sample size, better quality and multicenter studies are required to fully elucidate this issue.