Viral factors influencing the outcome of human cytomegalovirus infection in liver transplant recipients
Section snippets
Background
Human cytomegalovirus (CMV) is one of the most common opportunistic viral infections following orthotopic liver transplantation (OLT), causing life-threatening illness in 5–10% of recipients.1, 2, 3, 4 The viral factors associated with clinical outcome of CMV infection post-OLT include initial viral load, replication kinetics and emergence of antiviral resistant strains.5, 6, 7, 8, 9 Other viral characteristics postulated to influence the course of post-OLT infection include CMV genotype,10
Objectives
Examine viral factors that influence CMV infection outcomes following valganciclovir prophylaxis or laboratory-guided preemptive therapy in OLT recipients.
Recruitment and randomisation
Adults undergoing OLT at the Liver Transplant Unit, Austin Health were recruited to a randomised study comparing valGCV prophylaxis with laboratory-guided preemptive therapy. The study was approved by the relevant ethics committees (Austin Health 01943, SESIAHS 06/029 and UNSW 06145) and patient consent obtained from all participants. Donor (D) and recipient (R) serostatus were determined pre-transplant. It is well established that prophylaxis is important in reducing the incidence of CMV
CMV infection and disease in D+R− OLT recipients receiving antiviral prophylaxis
Despite receiving prophylaxis, most (80%) D+R− recipients were infected with CMV post-transplant, and over half developed a persistent CMV infection with high viral load (Table 1). DNAemia usually developed following cessation of prophylaxis, but persistent infection was detected during prophylaxis for 5/15 recipients. CMV infection progressed to clinical disease for 3/15 D+R− recipients. One patient given valGCV prophylaxis immediately following transplantation, developed CMV hepatitis
Discussion
Transplantation from seropositive donors to seronegative recipients (D+R−) continues to be the major risk factor for development of CMV disease post-OLT, despite valGCV prophylaxis. Although insignificant due to low numbers, our results show delayed initiation of prophylaxis potentially contributes to worse outcomes for these recipients, and early, reduced dosage of valGCV may be a better strategy for prevention of CMV in recipients with renal impairment. The shortage of CMV seronegative donors
Conflict of interest
No conflict of interest.
Ethical approval
This study was approved by the ethics committees of Austin Health (01943), SESIAHS (06/029) and UNSW (06145).
Acknowledgements
The technical assistance of Zubair Waliuzzaman, Nikolas Rismanto and Catherine Smith and financial support of Roche Products, Australia is acknowledged with appreciation. This study is registered by ANZCTR (http://www.ANZCTR.org.au/ACTRN12610000787088.aspx) ACTRN: ACTRN12610000787088.
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Cited by (14)
Cytomegalovirus specific polyfunctional T-cell responses expressing CD107a predict control of CMV infection after liver transplantation
2022, Cellular ImmunologyCitation Excerpt :In this cohort, the loss of immune function allows the virus to replicate unchecked, leading to viremia and ultimately disease [7]. Indeed, many studies have found an association between CMV infection and a worse post-transplant outcome following organ transplantation [9–18]. Several factors have been implicated in the development of CMV infection after LT. The most important one is the donor (D) and recipient (R) serological status, used to define different susceptibility categories; a high risk of infection is predicted in CMV seronegative recipients receiving a positive donor organ, due to lack of CMV immunity.
Infectious diseases of the hepatobiliary system
2020, Diagnostic HistopathologyCitation Excerpt :Where the donor and recipient are both positive, or the recipient is positive and the donor negative, reactivation can still occur but timely laboratory assays allow prophylaxis to be delayed until significant CMV levels are detected. Some patients can then avoid the potential side effects of another drug and the emergence of drug resistant strains may be minimised.30 Herpes simplex viruses types 1 and 2 can cause a necrotising hepatitis, usually in the immunosuppressed, severe enough to warrant transplantation.
Clinical significance of human cytomegalovirus viruria and the effect of antiviral therapy in hematopoietic stem cell transplant recipients
2019, Journal of Microbiology, Immunology and InfectionCitation Excerpt :One reason is that most of the patients in our study received antiviral treatment too late. Unlike serum antigen or antibody tests, the results of which can be obtained immediately, it usually takes days or even weeks for CMV to be isolated from cell culture.19 A treatment strategy based on detection of CMV through the convention cell culture system may not be timely enough to prevent tissue damage caused by the virus.
Infectious diseases of the hepatobiliary system
2017, Diagnostic HistopathologyCitation Excerpt :Where the donor and recipient are both positive, or the recipient is positive and the donor negative, reactivation can still occur but timely laboratory assays allow prophylaxis to be delayed until significant CMV levels are detected. Some patients can then avoid the potential side effects of another drug and the emergence of drug resistant strains may be minimised.31 Herpes simplex viruses types 1 and 2 can cause a necrotising hepatitis, usually in the immunosuppressed, severe enough to warrant transplantation.
Prospective study on CMV-reactivations under preemptive strategy in CMV-seropositive adult liver transplant recipients
2013, Journal of Clinical VirologyCitation Excerpt :Compared with our previous series, by using a pre-emptive strategy the incidence of CMV viraemia has decreased from 46% to 39% and the incidence of CMV hepatitis from 9% to <2%.14 In another recent study, laboratory-guided pre-emptive therapy was demonstrated to effectively control CMV infection and prevent CMV disease in (R+) liver-transplant recipients.16 Our results demonstrate that most CMV-seropositive liver recipients do not develop CMV replication, and even if reactivations occur, most of them are temporal, self-limiting, low-level DNAaemias.
Infectious diseases of the hepatobiliary system
2013, Diagnostic HistopathologyCitation Excerpt :Where the donor and recipient are both positive, or the recipient is positive and the donor negative, reactivation can still occur but timely laboratory assays allow prophylaxis to be delayed until significant CMV levels are detected. Some patients can then avoid the potential side effects of another drug and the emergence of drug resistant strains may be minimized.34 Herpes simplex viruses types 1 and 2 can cause a necrotizing hepatitis, usually in the immunosuppressed, severe enough to warrant transplantation.