Cytomegalovirus Infection Following Liver Transplantation: Review of the Literature (original) (raw)
Related papers
Cytomegalovirus infection in orthotopic liver transplantation
Transplant International, 1989
We retrospectively studied 175 orthotopic liver transplants in 151 patients. Of the 151 patients, 59 (39.1 %) were diagnosed as having cytomegalovirus (CMV) infection. The rate of infection in patients treated for rejection was 48.8% as compared to 26.2% in patients without rejection (P< 0.01). Antirejection therapy was associated with culture-positive cases in 33 out of 43 patients as compared to 9 out of 16 patients who had CMV antibody titer elevations. Patients were treated with gancyclovir if they had simultaneous positive cultures from multiple sites and were seriously ill. Eighteen of the 19patients thus treated had side effects, one of which was senous (bone marrow hypoplasia). Cultures became negative in 15 out of 17 (88%) of the surviving patients. Patient survival was similar to our overall survival rate of 87%.
Cytomegalovirus infection as a common complication following liver transplantation
Transplantation Proceedings, 2003
The aim of our study was to assess the incidence course, influence on liver function, diagnostic methods, prophylaxis of, and cost treatment effectiveness of CMV infection among 123 consecutive liver transplant recipients. All patients received immunoglobulin and parenterall gancyclovir as prophylaxis. CMV IgM and IgG antibodies were determined using an ELISA method. Thirty seven patients (30.0%) developed CMV infection. Main indications for primary LTX were: immune liver disease (n ϭ 22), viral hepatitis (n ϭ 5), and other (n ϭ 10). CMV infection occurred between the days 5 and 416. Ten patients (27.0%) developed more than one infection (52 infections in total). Asymptomatic CMV infection was diagnosed in six cases (16.2%), CMV syndrome in 11 cases (29.7%), and hepatitis in 35 cases. All patients were treated with gancyclovir and immunoglobulin (18 cases). The intensity of infection was mild or moderate. There was no case of pneumonia or neurological disease, nor the need to use foscarnet. The correlations between the incidence of CMV infection and acute rejection, tacrolimus versus cyclosporine regimens, dual versus triple immunosupressive schemes were not statistically significant, whereas anti-IL-2R-ab antibodies markedly reduced the incidence of CMV infection (P Ͻ .05). The values of CMV IgM significantly differred before/during infection (P Ͻ .001) and before/after infection (P Ͻ .05). In conclusion, prophylaxis and antiviral treatment result in a mild or moderate intensity of CMV infection with acceptable costs. Among immunosuppressive drugs, only anti-IL-2Rab was proved to significantly reduce the incidence of CMV.
Prevention and treatment of cytomegalovirus infection in organ transplant recipients
Transplant Infectious Disease, 1999
recipients Abstract: Cytomegalovirus (CMV) is the most common viral pathogen in organ transplant recipients. The patients at highest risk of developing CMV disease are seronegative recipients of seropositive donors, and seropositive recipients who receive antilymphocyte agents such as OKT3 and antithymocyte globulin (ATG) for induction or for rejection. There have been many trials of CMV prevention, but they are difficult to compare with one another because of variability in definitions and end points. Two modalities that have been used to prevent CMV disease are prophylaxis and preemptive therapy. In prophylaxis all patients are given an antiviral agent in order to prevent CMV disease, while in preemptive therapy (also called targeted prophylaxis) only patients who are identified as 'high risk' are selected for treatment. Selected trials of prophylaxis and preemptive therapy in solidorgan recipients are reviewed. The factors to be considered in using one modality or the other are side effects from antivirals, cost of monitoring and antivirals, efficacy of the two modalities, and potential emergence of drug resistance. Sensitive tests that have been used for early diagnosis and monitoring of CMV are antigenemia and the polymerase chain reaction (PCR). Antigen pp65 is a lower matrix protein and can be detected in peripheral blood leukocytes. The sensitivity and specificity are high and vary from 89% to 100% and 92% to 96%, respectively. Currently, many authors believe that the antigenemia test is more useful than the PCR test. The antigenemia test is useful for viral monitoring as a guide for preemptive therapy after organ transplantation. Persistence of high counts of antigenemia may indicate inadequate antiviral therapy or emergence of resistance. Recurrence of positive antigenemia after treatment of CMV disease can be a sign of relapse. Transplant patients who develop resistance to antiviral drugs are usually seronegative recipients who receive an organ from a seropositive donor and have several courses of antivirals for CMV disease. Ganciclovir is the most frequent antiviral agent used in transplant recipients and is usually well tolerated. Resistance to ganciclovir may occur and is usually secondary to virus mutation in the UL97 gene. The availability of sensitive diagnostic tests such as pp65 antigenemia has made the early diagnosis of CMV possible in organ transplant recipients. CMV is being treated much earlier now, and progression to disseminated disease is uncommon. Prudent use of antiviral drugs will hopefully limit the problem of drug resistance.
Impact of cytomegalovirus prophylaxis on rejection following orthotopic liver transplantation
Liver Transplantation, 2005
With improved cytomegalovirus (CMV) prophylaxis, CMV disease after liver transplantation has decreased dramatically, and patient and graft survival have improved. We examined the impact of CMV prophylaxis on biopsy proven rejection after orthotopic liver transplantation by analyzing data on 192 liver recipients over 5 years (1994)(1995)(1996)(1997)(1998)(1999). Risk factors assessed for biopsy proven rejection including donor and recipient age, CMV serostatus; CMV prophylaxis; immunosuppression; bacteremia and blood product use were examined over a 2-year follow-up. Multivariate analysis of risk factors for rejection showed that bacteremia (HR 3.57, 95% CI 1.39-9.36, P,)800.0؍ donor age (HR 1.20, 95% CI 1.06-1.36, per 10 year increase, P,)400.0؍ and use of cyclosporine as initial immunosuppression compared to tacrolimus (HR 1.98, 95% CI 1.27-3.09, P)300.0؍ were associated with increased risk; ganciclovir prophylaxis for 3 months (HR 0.51, 95% CI 0.33 to 0.79, P)300.0؍ and recipient age (HR 0.78; 95% CI 0.63-0.96, for each 10 year increase, P)30.0؍ were associated with decreased risk. We conclude that, the use of CMV prophylaxis with ganciclovir significantly reduces the incidence of biopsy proven rejection in liver transplant recipients. (Liver Transpl 2005; 11:1597-1602
Transplant International, 2013
Cytomegalovirus (CMV) is a major cause of morbidity and mortality following solid organ transplantation (SOT). Two strategies, prophylactic, and preemptive have emerged for the prevention of CMV infection and disease after SOT. This retrospective chart review of two liver transplant cohorts: prophylactic and preemptive, compares the clinical impact of transitioning from prophylactic to preemptive strategy. The primary outcome is the incidence of CMV viremia at 3-and 6-months post-transplant. Secondary outcomes include: incidence of CMV tissue-invasive disease, acute cellular rejection, leukopenia and neutropenia, opportunistic infection rates, hospital readmission rates, and mortality at 3-and 6-months post-transplant. A total of 109 patients were included in the analysis. The incidence of CMV viremia was 4.9% and 50.0% (P < 0.001) in the prophylactic versus preemptive cohort, respectively, at 3 months post-transplant. The incidence of CMV viremia was 24.6% and 8.3% (P = 0.026) in the prophylactic versus preemptive cohort, respectively, at 6 months post-transplant. There were no statistical significant differences in the secondary outcomes between both cohorts. In conclusion, there is a statistical significant difference in time to onset of CMV viremia; however, the use of either prophylactic or preemptive strategy was not associated with significant negative clinical outcomes of CMV.
Transplantation, 1998
In a cohort of 43 liver transplant recipients who did not receive antiviral prophylaxis, qualitative and quantitative polymerase chain reactions (PCRs) from peripheral blood were prospectively compared to determine their value in the diagnosis of established cytomegalovirus (CMV) disease and for the early detection of CMV replication as a marker for preemptive antiviral therapy. Using a cutoff of 7000 copies of CMV DNA per sample, the specificity and positive predictive values of qualitative PCR for the diagnosis of established CMV disease increased from 33% to 89% and from 54% to 82%, respectively, without reducing the 100% sensitivity and negative predictive value. By contrast, quantification of viral load provided no additional advantage to qualitative PCR for the early diagnosis of CMV infection before development of disease.
Transplant Infectious Disease, 2006
The most common organ-specific manifestation of cytomegalovirus (CMV) infection after liver transplantation is hepatitis. Here we retrospectively describe the detailed virological, histological, immunological, and clinical findings associated with CMV infection in 229 consecutive adult liver transplantation patients. CMV infection was diagnosed by pp65 antigenemia. From 439 liver biopsies, CMV antigens were demonstrated by immunohistochemistry and CMV DNA by hybridization. The Banff criteria were used for histology. The expression of various adhesion molecules (intercellular adhesion molecule-1 [ICAM-1], vascular cell adhesion molecule-1 [VCAM-1], endothelial leukocyte adhesion molecule-1 [ELAM-1]), their ligands (leukocyte function antigen-1 [LFA-1], very late antigen-4 [VLA-4], Sialyl-LewisX-molecule [SLeX]), and lymphoid activation markers (major histocompatibility complex [MHC] Class II, interleukin-2-receptor [IL-2R]) was demonstrated by immunohistochemistry. CMV infection of the transplant occurred in 26 patients (11% of all 229 patients and 17% of the 151 patients with liver biopsy). The incidence was higher among seronegative (26%) than in seropositive recipients (9%), but most cases 18/26 (70%) were reactivations. The CMV pp65 antigenemia levels were usually high in primary infections (893+/-1069, range 50-3000 pp65+cells), but varied widely in reactivations (388+/-740, range 3-3000). The histological Banff score was slightly increased (2.3+/-0.9). Microabscesses, lymphocytic infiltration, Kupffer cell reaction, and parenchymal alterations were common but viral inclusions rare. CMV significantly (P<0.05) increased ICAM-1 and VCAM-1 expression and the number of LFA-1, VLA-4, and Class II-positive lymphocytes in the graft. All CMV infections were successfully treated with antivirals. Intragraft CMV infection had no influence on the long-term outcome, but biliary complications were common. In conclusion, CMV infection of the liver transplant occurred both in primary infection and in reactivation, and also in the cases with low pp65 antigenemia levels. Microabscesses and other histological alterations were common but viral inclusions rare. Increased adhesion molecule expression was associated with lymphocyte infiltration. Successfully treated CMV hepatitis had no influence on the long-term clinical outcome.
Liver Transplantation, 2012
It is believed that antiviral prophylaxis decreases the incidence of cytomegalovirus (CMV) reactivation and disease. There are few data regarding weekly assays for CMV DNA after transplantation and the subsequent management of CMV. Here we report a cohort of living related liver transplantation (LRLT) patients who were treated for invasive CMV disease or for CMV infections if they were receiving steroids for rejection. Patients who underwent liver transplantation at our center between September 2006 and August 2010 and were recipient-positive/donor-positive (R þ /D þ ) were prospectively included. Patients were tested for CMV DNA 3 weeks after transplantation. CMV DNA-positive patients underwent weekly DNA monitoring until there were 2 consecutive negative reports. Those who developed CMV disease or had rising DNA titers while they were on treatment for rejection were treated. A Cox regression analysis was performed for factors predicting survival. Two hundred sixty-six of the 306 R þ /D þ patients were CMV DNA-negative 3 weeks after transplantation, and 40 had detectable DNA. One of the DNA-negative patients developed CMV disease after treatment for rejection with methylprednisolone. Thirty patients had <500 copies/mL, and 10 had !500 copies/mL. Two of the 30 patients with DNA levels < 500 copies/mL developed CMV disease. Six of the 10 patients with DNA levels !500 copies/mL developed disease. CMV disease occurred in 9 of the 306 patients (2.9%). One patient received treatment for a rise in DNA titers while he was receiving steroids. There was a significant correlation between steroid administration for acute cellular rejection (ACR) and CMV reactivation (P ¼ 0.003) and disease (P ¼ 0.002). A multivariate analysis showed that CMV reactivation/disease did not predict survival. There was no difference in survival between CMV DNA-positive patients and CMV DNA-negative patients (P ¼ 0.68). In conclusion, CMV reactivation is common after LRLT (13%), but the disease is rare (2.9%) without prophylaxis in CMV immunoglobulin G-positive recipients. The administration of steroids for ACR strongly correlates with CMV reactivation and disease. CMV reactivation and disease did not affect survival in our patient cohort.