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Cytomegalovirus infection in liver transplant recipients: updates on clinical management.

ABSTRACT: Cytomegalovirus (CMV) infection is a common complication after liver transplantation, and it is associated with multiple direct and indirect effects. Management of CMV infection and disease has evolved over the years, and clinical guidelines have been recently updated. Universal antiviral prophylaxis and a pre-emptive treatment strategy are options for prevention. A currently-recruiting randomized clinical trial is comparing the efficacy and safety of the two prevention strategies in the highest risk D+R- liver recipients. Drug-resistant CMV infection remains uncommon but is now increasing in incidence. This highlights the currently limited therapeutic options, and the need for novel drug discoveries. Immunotherapy and antiviral drugs with novel mechanisms of action are being investigated, including letermovir (AIC246) and brincidofovir (CMX001). This article reviews the current state of CMV management after liver transplantation, including the updated practice guidelines, and summarizes the data on investigational drugs and vaccines in clinical development.

SUBMITTER: Marcelin JR

PROVIDER: S-EPMC4138447 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Cytomegalovirus infection in liver transplant recipients: updates on clinical management.

Marcelin Jasmine Riviere JR Beam Elena E Razonable Raymund R RR

World journal of gastroenterology 20140801 31

Cytomegalovirus (CMV) infection is a common complication after liver transplantation, and it is associated with multiple direct and indirect effects. Management of CMV infection and disease has evolved over the years, and clinical guidelines have been recently updated. Universal antiviral prophylaxis and a pre-emptive treatment strategy are options for prevention. A currently-recruiting randomized clinical trial is comparing the efficacy and safety of the two prevention strategies in the highest ...[more]

PMID: 25152570

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Project description:Cytomegalovirus (CMV) is one of the most common viral pathogens causing clinical disease in liver transplant recipients, and contributing to substantial morbidity and occasional mortality. CMV causes febrile illness often accompanied by bone marrow suppression, and in some cases, invades tissues including the transplanted liver allograft. In addition, CMV has been significantly associated with an increased predisposition to acute and chronic allograft rejection, accelerated hepatitis C recurrence, and other opportunistic infections, as well as reduced overall patient and allograft survival. To negate the adverse effects of CMV infection on transplant outcome, its prevention, whether through antiviral prophylaxis or preemptive therapy, is an essential component to the management of liver transplant recipients. Two recently updated guidelines have suggested that antiviral prophylaxis or preemptive therapy are similarly effective in preventing CMV disease in modest-risk CMV-seropositive liver transplant recipients, while antiviral prophylaxis is the preferred strategy over preemptive therapy for the prevention of CMV disease in high-risk recipients [CMV-seronegative recipients of liver allografts from CMV-seropositive donors (D+/R-)]. However, antiviral prophylaxis has only delayed the onset of CMV disease in many CMV D+/R- liver transplant recipients, and such occurrence of late-onset CMV disease was significantly associated with increased all-cause and infection-related mortality after liver transplantation. Therefore, a search for better strategies for prevention, such as prolonged duration of antiviral prophylaxis, a hybrid approach (antiviral prophylaxis followed by preemptive therapy), or the use of immunologic measures to guide antiviral prophylaxis has been suggested to prevent late-onset CMV disease. The standard treatment of CMV disease consists of intravenous ganciclovir or oral valganciclovir, and if feasible, reduction in pharmacologic immunosuppression. In one clinical trial, oral valganciclovir was as effective as intravenous ganciclovir for the treatment of mild to moderate CMV disease in solid organ (including liver) transplant recipients. The aim of this article is to provide a state-of-the art review of the epidemiology, diagnosis, prevention, and treatment of CMV infection and disease after liver transplantation.

Project description:BackgroundTriplex vaccine was developed to enhance cytomegalovirus (CMV)-specific T cells and prevent CMV reactivation early after hematopoietic stem cell transplant (HCT).ObjectiveTo determine the safety and efficacy of Triplex.DesignFirst-in-patient, phase 2 trial. (ClinicalTrials.gov: NCT02506933).Setting3 U.S. HCT centers.Participants102 CMV-seropositive HCT recipients at high risk for CMV reactivation.InterventionIntramuscular injections of Triplex or placebo were given on days 28 and 56 after HCT. Triplex is a recombinant attenuated poxvirus (modified vaccinia Ankara) expressing immunodominant CMV antigens.MeasurementsThe primary outcomes were CMV events (CMV DNA level ≥1250 IU/mL, CMV viremia requiring antiviral treatment, or end-organ disease), nonrelapse mortality, and severe (grade 3 or 4) graft-versus-host disease (GVHD), all evaluated through 100 days after HCT, and grade 3 or 4 adverse events (AEs) within 2 weeks after vaccination that were probably or definitely attributable to injection.ResultsA total of 102 patients (51 per group) received the first vaccination, and 91 (89.2%) received both vaccinations (46 Triplex and 45 placebo). Reactivation of CMV occurred in 5 Triplex (9.8%) and 10 placebo (19.6%) recipients (hazard ratio, 0.46 [95% CI, 0.16 to 1.4]; P = 0.075). No Triplex recipient died of nonrelapse causes during the first 100 days or had serious AEs, and no grade 3 or 4 AEs related to vaccination were observed within 2 weeks after vaccination. Incidence of severe acute GVHD after injection was similar between groups (hazard ratio, 1.1 [CI, 0.53 to 2.4]; P = 0.23). Levels of long-lasting, pp65-specific T cells with effector memory phenotype were significantly higher in Triplex than placebo recipients.LimitationThe lower-than-expected incidence of CMV events in the placebo group reduced the power of the trial.ConclusionNo vaccine-associated safety concerns were identified. Triplex elicited and amplified CMV-specific immune responses, and fewer Triplex-vaccinated patients had CMV viremia.Primary funding sourceNational Cancer Institute and Helocyte.

Project description:Medication nonadherence after liver transplantation (LT) is associated with adverse clinical outcomes such as graft rejection and graft loss. Few studies have examined nonadherence and its impact on clinical outcomes in LT. The study objectives were (1) to evaluate medication understanding (with treatment knowledge and demonstrated regimen use scores) and medication adherence or nonadherence to entire regimens among LT recipients and (2) to examine associations of these exposures with clinical outcomes. We conducted a 2-site study of 105 recipients between 2011 and 2012 at 2 transplant centers in Chicago, IL and Atlanta, GA. Data were collected via detailed, in-person interviews and medical record reviews. Study participants were middle-aged and predominantly male; 15% of the sample had limited literacy. On average, patients were taking 11 medications [standard deviation (SD)?=?4], and 39% had undergone a medication change within the last month. The average scores for the entire medication regimen were 86% (SD?=?22%) for treatment knowledge and 78% (SD?=?22%) for demonstrated regimen use. The mean score for self-reported nonadherence to the entire regimen was 14% (SD?=?20%), whereas 32% of the patients were nonadherent according to tacrolimus levels. In multivariate analyses, lower income, less time since transplantation, a higher number of medications, and limited literacy were inversely associated with treatment knowledge scores (all P?<?0.05), whereas limited literacy was associated with nonadherence according to tacrolimus levels (P?<?0.05). In multivariate models, higher scores for treatment knowledge [incidence rate ratio (IRR)?=?0.85, 95% confidence interval (CI)?=?0.74-0.97] and demonstrated regimen use (IRR?=?0.87, 95% confidence interval?=?0.77-0.98) were independently associated with 15% and 13% reductions in the number of posttransplant rehospitalizations, respectively. Inadequate treatment knowledge and improper regimen use may be significant determinants of unintentional nonadherence among LT recipients and are associated with adverse clinical outcomes.

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Cytomegalovirus infection in liver transplant recipients: updates on clinical management.

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Cytomegalovirus infection in liver transplant recipients: updates on clinical management.

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