Comparison of cytomegalovirus pp-65 antigenemia assay and plasma DNA correlation with the clinical outcome in transplant recipients

The relationship between quantitative antigenemia and plasma DNAemia was studied for monitoring cytomegalovirus (CMV) viremia in CMV infection (CMVI) or disease (CMVD), in 20 transplant recipients (13 CMD, seven CMVI). A total of 142 samples of blood were assayed for CMV-DNA and pp-65 antigenemia (CMV-Ag). A quantitative correlation between both markers was found (P < 0.0001). First CMV antigenemia as well as first plasma DNA viral load was similar in CMVI and CMVD (29 vs. 24 CMV-Ag+ cells/10(5) PMN; and 7445 vs. 12407 CMV-DNA copies/ml). The maximum antigenemia was higher in CMVD than in CMVI (146 +/- 87 vs. 61 +/- 54 +cells/10(5) PMN, P < 0.05), but the highest CMV plasma viral load was similar in both groups (62592 +/- 33000 vs. 42055 +/- 38600 copies/ml). In nine patients, maximum antigenemia coincided with highest plasma DNA viral load, but in 10 highest DNAemia occurred 6 days later. On the contrary, antigenemia declined faster than CMV-DNAnemia, after treatment.     

Antigenemia for cytomegalovirus in renal transplantation: choosing a cutoff for the diagnosis criteria in cytomegalovirus disease

Cytomegalovirus (CMV) infection is a frequent complication in transplant recipients, causing a high level of morbidity and mortality. We studied 203 consecutive renal transplant recipients performed between January 2000 and December 2001. Patients underwent weekly measurements of CMV pp65 antigen to assess CMV activity from the 4th to the 12th week posttransplantation. The results were reported as number of cells positive for the pp65 antigen among 10(5) granulocytes. In order to define a best cutoff to diagnose CMV disease with desirable sensitivity and specificity, we used a receiver operator characteristics (ROC) curve. The cutoff of four positive cells corresponded to a sensitivity of 93% and specificity of 60% (AUC = 0.87) for the diagnosis of CMV disease. The chosen cutoff for starting antiviral treatment was 10 cells, since this was associated with a sensitivity of 92% and specificity of 70% (AUC = 0.90). In conclusion, the highly sensitive cutoff points for the diagnosis of antigenemia was four cells and 10 cells for initiation of antiviral therapy.     

Efficacy and safety of valgancyclovir as preemptive therapy for the prevention of cytomegalovirus disease in solid organ transplant recipients

We prospectively followed 70 CMV-seropositive solid organ transplant recipients to evaluate the efficacy and safety of valganciclovir (VGCV) as preemptive therapy based on antigenemia test to prevent cytomegalovirus (CMV) disease. From December 2003 to May 2004, 12 of 70 (17%) asymptomatic patients who showed an antigenemia value > or =25 positive cells per 2 x 10(5) polymorphonuclear (PMN) were treated with VGCV (900 mg twice a day adjusted to renal function) until resolution of CMV antigenemia, a minimum of 14 days. No patient developed CMV disease during follow-up. Only one who showed an asymptomatic relapse of the antigenemia test > or =25 positive cells was successfully treated with a repeated course of VGCV. Mean duration of VGCV therapy was 18 days (range, 14 to 28). Antigenemia was negative in 7 of 12 (58%) patients after 14 days and negative in all patients 4 weeks after the administration of VGCV. No significant side effects were associated with the use of VGCV therapy. Preemptive VGCV therapy is safe and effective in the prevention of CMV disease in seropositive solid organ transplant recipients.     

Cytomegalovirus infection after renal transplantation: selective prophylaxis and treatment

We have reviewed our experience in selective cytomegalovirus (CMV) infection prophylaxis and treatment in our renal transplant population. Between 1996 and 2001, 263 cadaveric renal transplant recipients had at least 6 months follow up. Immunosuppression was based on cyclosporine Neoral (n=108) or tacrolimus (n=155). CMV infection prophylaxis (oral acyclovir or gancyclovir at half usual doses) was only prescribed in recipients receiving a CMV positive ve kidney and in recipients treated with OKT3. CMV infection was diagnosed by a positive pp65 antigenemia upon appearance of CMV-related symptoms, leading to specific treatment (IV ganciclovir) only if symptoms were intense or there was visceral involvement. Thus, no preemptive treatment or programmed or periodic antigenemia was performed in any case. Nineteen episodes of symptomatic CMV infection were diagnosed (prevalence 7.2%). The frequency was similar for all immunosuppressive regimens. Only 9 of 19 (47%) of patients were given IV ganciclovir; the others were not treated. All patients survived without apparent complications, relapses, or recurrences. No oral gancyclovir was delivered after IV treatment. Our CMV prophylaxis protocol was limited to high-risk patients, using lower gancyclovir dosages than those usually advocated. It does not include programmed or scheduled search for CMV antigenemia in asymptomatic renal transplant patients. Despite these factors, our CMV infection rate and severity were similar to those reported with more aggressive protocols, with extended prophylaxis, preemptive therapy, or intense surveillance.     

Real-time PCR assay compared with antigenemia assay for detecting cytomegalovirus infection in kidney transplant recipients

Human cytomegalovirus (CMV) infection is a major cause of morbidity and mortality among kidney transplant recipients. The CMVpp65 antigenemia assay has been used for preemptive therapy. Real-time polymerase chain reaction (PCR) technology for CMV DNA quantification in blood has demonstrated a good correlation with the currently employed CMV antigenemia assay. In this study, 90 renal transplant recipients were prospectively enrolled from July 2004 and May 2005. Monitoring of CMV infection was routinely performed with CMV antigenemia and real-time PCR assays. Real-time plasma PCR and CMV antigenemia assays were assessed on 797 samples. CMV antigenemia correlated with a positive CMV PCR (chi(2) = 78.05; P < .0001). Not only the positive rate but also the number of positive cells correlated with the number of PCR DNA copies (F = 26.07, r(2) = .25, P < .0001). To define an optimal cutoff value of CMV DNA load to initiate treatment in kidney transplant patients, we considered a CMV antigenemia titer of >50 positive cells per 400,000 leukocytes as the gold standard in our previous study. The optimal cutoff value for the quantitative real-time PCR assay was predicted to be 86 copies/microL. Thus, we observed that CMV real-time PCR assay would not completely replace antigenemia assay in kidney transplant recipients, but can be used complementarily to screen antigenemia and monitor preemptive therapy.     

Cytomegalovirus disease latent and active infection rates during the first trimester after kidney transplantation

Cytomegalovirus (CMV) infection is the single most frequent infectious complication in renal transplant recipients. The aim of this study was to determine the incidence of latent and active infections with CMV during the first 3 months after kidney transplantation. From January 2000 to December 2001, 203 consecutive adult renal transplant recipients underwent weekly measurements of pp65 CMV antigen from the 4th to the 12th posttransplantation week. Latent infection (seropositivity) was found in 92% of the population. Primary infection occurred in 4.9% (10 of 203), among whom 66% were previously seronegative patients. Among the primary infection patients, 70% (7 of 10) developed severe disease. The overall incidence of viremia was 69.5%, being more frequent among cadaver recipients (79% vs 59%; P =.02). The overall incidence of CMV disease was 38.4% (78 of 203) with 24.6% classified as severe disease requiring antiviral therapy. In conclusion, our population showed a high prevalence of latent infection with viremia. Not all patients developed clinical disease. Most subjects experienced a mild spectrum of symptoms, probably due to the prospective search for active infection during the major risk period after kidney transplantation.     

Monitoring and detection of cytomegalovirus in liver transplant recipients

Cytomegalovirus (CMV) is a β-herpesvirus. CMV infections are a common complication contributing to morbidity and mortality after liver transplantation. Among organ transplant recipients, CMV can reactivate from latency during the first 6 months. This prospective study performed from February 2008 to December 2009 examined liver transplant recipients during the first 6 months. Two methods were performed to detect CMV infections: antigenemia (AGM) and nested (PCR). Ninety-four patients, including 72 men (76.6%) and 22 women (23.4%) underwent liver transplantation during this period. We analyzed 575 samples including 465 for AGM and PCR. Forty-three (9.25%) showed positive AGM as detected 2 to 179 days posttransplantation with a mean of 50 days and a median of 35 days, and 93/465 (20%) showed positive PCR at 0 to 186 days posttransplantation with a mean of 31 days and a median of 38 days. Among the 43 antigenemia patients, 38 samples were positive for up to 5 cells 18 of which were PCR-positive. Five samples were positive with more than 5 cells, including 3 that were PCR-positive. Only 4.51% had AGM and were PCR-positive in the same sample. Despite only 9.25% (43/465) showing AGM, the current study suggested the utility of routine monitoring to detect early CMV infection among liver transplantation patients seeking to reduce morbidity and mortality.     

Abstension from treatment of low-level pp65 cytomegalovirus antigenemia after liver transplantation: a prospective study

BACKGROUND: Ganciclovir is a highly effective and relatively safe drug to treat cytomegalovirus (CMV) infection in liver transplant patients; CMV resistance to ganciclovir is progressively emerging due to the extensive use of the drug in transplant and AIDS patients; CMV pp65 antigenemia allows early diagnosis of CMV infection and quantitation of the viral load; preemptive antigenemia-guided therapy of CMV infection can prevent CMV disease but the threshold of antigenemia value above which treatment has to be instituted is unclear. METHODS: To demonstrate the safety of abstention from preemptive treatment in the presence of low levels of antigenemia 77 consecutive liver transplant recipients were prospectively evaluated. Antigenemia was tested twice a week from transplantation until discharge, then once a week until the third postoperative month. In absence of risk factors for CMV disease, namely donor positive/recipient negative CMV serology, treatment with antibodies to lymphocytes and retransplantation, only patients with antigenemia of more than 50 or symptoms possibly related to CMV infection had preemptive treatment. RESULTS: A total of 32 patients had at least one positive antigenemia test with a value less than 50; 22 (68.7%) spontaneously cleared the virus, 3 were treated with i.v. ganciclovir for the presence of fever, and the other 7 (21,8%) progressed to values of antigenemia of more than 50 and were treated even if asymptomatic. No CMV disease was observed in these patients. CONCLUSION: CMV antigenemia less than 50 in liver transplant recipients with low and intermediate risk for CMV disease does not mandate preemptive ganciclovir treatment. Close surveillance with repeated determination of antigenemia until its negativization and careful clinical and laboratory monitoring is advisable.     

Cytomegalovirus prophylaxis with intravenous polyvalent immunoglobulin in high-risk renal transplant recipients

Cytomegalovirus (CMV) seronegative renal allograft recipients (R-), particularly those with a graft from a CMV-seropositive donor (D+), are at high risk for primary CMV infection. CMV resistance to antiviral oral therapy is an emerging problem in renal transplantation, prompting development of new prophylactic strategies. We retrospectively studied the 1-year posttransplantation incidence of CMV infection in high-risk renal transplant recipients, in whom polyvalent intravenous immunoglobulins (IVIg) were used as prophylaxis. Forty R- patients received immunoprophylaxis by polyvalent IVIg (0.25 g/kg weekly for 8 weeks, starting on the operative day). CMV serological tests remained negative in eight patients (20%). Eight patients (20%) had asymptomatic CMV infection while 24 (60%) developed CMV syndrome and were treated with gancyclovir (10 mg/kg/day intravenously for 3 weeks). None had CMV disease or opportunistic infection. Six patients (15%) had biopsy-proven acute rejection, which followed CMV syndrome in three cases. One-year renal allograft and patient survivals were 95% and 97.5%, respectively. Mean serum creatinine level was 124 +/- 33 micromol/L at 1 year. Clinical tolerance of IVIg was excellent, without any episode of acute renal failure. Polyvalent IVIg provides effective prophylaxis in renal transplant recipients at high risk for CMV infection and is associated with excellent 1-year allograft survival. Because of their immunomodulatory functions, IVIg may have a beneficial effect on the incidence of acute and chronic rejection and allograft survival. A randomized prospective study is required to evaluate long-term effects of CMV prophylaxis with polyvalent IVIg compared to antiviral agents in renal transplant recipients.     

Treatment of cytomegalovirus infection or disease in solid organ transplant recipients with valganciclovir

Valganciclovir (VGC) has proved efficacious and safe for the prophylaxis against cytomegalovirus (CMV) in high-risk transplant recipients and for the treatment of CMV retinitis in AIDS patients. We used VGC for the treatment of CMV infection (viremia without symptoms) or disease (CMV syndrome or tissue-invasive disease) in kidney, heart, and lung transplant recipients. Fourteen transplant recipients were treated: five for asymptomatic CMV infection and nine for CMV disease. VGC was administered in doses adjusted to renal function for 4 to 12 weeks (induction and maintenance therapy). Clinically, all nine patients with CMV disease responded to treatment. Microbiologically, treatment with VGC turned blood culture negative for CMV within 2 weeks in all patients and was associated with a > or =2 log decrease in blood CMV DNA within 3 weeks in 8 of 8 tested patients. With a follow-up of 6 months (n = 12 patients), asymptomatic recurrent CMV viremia was noted in five cases, and CMV syndrome noted in one case (all cases in the first 2 months after the end of treatment). VGC was clinically well tolerated in all patients; however, laboratory abnormalities occurred in three cases (mild increase in transaminases, thrombocytopenia, and pancytopenia). This preliminary experience strongly suggests that therapy with VGC is effective against CMV in organ transplant recipients; however, the exact duration of therapy remains to be determined: a longer course may be necessary to prevent early recurrence.     

Long-term oral ganciclovir prophylaxis for prevention of cytomegalovirus infection and disease in cytomegalovirus high-risk renal transplant recipients

BACKGROUND: Although specific therapy is available with ganciclovir, cytomegalovirus (CMV) disease remains a major problem after renal transplantation especially in CMV seronegative recipients of organs of seropositive donors (D+R-). METHODS: In an open-labeled prospective controlled trial we evaluated the effect of long-term oral ganciclovir prophylaxis (3 g/day for 3 months posttransplantation) in a cohort of 31 CMV-high risk (D+R-) renal transplant recipients (GC) compared with a cohort of 28 high-risk patients with targeted CMV prophylaxis (CO) receiving i.v. ganciclovir during antirejection therapy. Primary end-points were CMV infection, diagnosed by pp65 antigenemia assay or serologic method, and CMV disease. Additionally severity of CMV disease quantified by a scoring system was evaluated. RESULTS: CMV prophylaxis significantly reduced the incidence of CMV infection (CO: 75%, GC: 45%; P<.05) and CMV disease (CO: 60%, GC: 29%; P<.05) without relevant side effects and without any clinical suspicion of ganciclovir resistance. Severity of CMV disease as quantified by a scoring system was reduced from 8.3+/-6.7 points in controls to 3.3+/-2.6 points in ganciclovir-treated patients (P<.05). Mortality did not differ significantly between the two groups (CO: n=3, GC: n=1; NS). However, there was one lethal CMV disease and a second death possibly attributable to CMV disease in the control group, whereas in ganciclovir-treated patients there was no CMV-associated fatal outcome. CONCLUSION: Long-term oral ganciclovir prophylaxis is effective and safe in CMV high-risk renal transplant recipients.     

Clinical usefulness of plasma quantitative polymerase chain reaction assay: diagnosis of cytomegalovirus infection in kidney transplant recipients

Background

Preemptive therapy is used to prevent cytomegalovirus (CMV) disease in transplant recipients. The CMV antigenemia assay, which has been commonly used as a predictive marker for preemptive therapy, requires intensive labor and immediate processing. We compared the cutoff value of plasma CMV polymerase chain reaction (PCR) with CMV antigenemia in kidney transplant recipients.

Methods

We compared two diagnostic methods for CMV infection in kidney transplant recipients: quantitative PCR (qPCR) versus antigenemia. We evaluated the optimal cutoff value of plasma CMV qPCR by using receiver-operating characteristic curves for specific antigenemia values. All kidney transplant recipients from January 2004 to January 2005 were enrolled and followed with CMV antigenemia and plasma CMV qPCR.

Results

The analyses were performed on 899 samples collected from 111 patients in the early posttransplant period, matching 84.1% of patients for the results of CMV antigenemia and plasma CMV qPCR. For patients with symptomatic CMV infection and disease, who showed ≥25 positive cells in the antigenemia assay, the cutoff value for qPCR was 17.8 copies/μL with a sensitivity of 97.1%, a specificity of 89.1%, and a positive predictive value of 26.6%.

Conclusions

Diagnostic assays for CMV such as CMV antigenemia and quantitative plasma PCR, showed similar diagnostic values. They are the methods of choice for the diagnosis and monitoring of active CMV infection after kidney transplantation. However, because of the relatively low positive predictive value of qPCR, this test may lead to unnecessary preemptive treatment in kidney transplant recipients.     

Cytomegalovirus antigenemia as a useful marker of symptomatic cytomegalovirus infection after renal transplantation--a report of 130 consecutive patients

In earlier work we demonstrated that CMV immediate early antigens can be detected in peripheral blood leukocytes of patients with active CMV infection. We now report a comparison of the antigenemia assay and an anti-CMV ELISA in a prospective longitudinal study of 130 renal transplant recipients who were monitored for active CMV infection during the first 3 months after transplantation. Active CMV infection developed in 56 patients. The antigenemia assay had a sensitivity of 89% and a specificity of 93% in the diagnosis of active CMV infection; for the ELISA these figures were 95 and 100%, respectively. In 22 of the 56 patients a CMV syndrome occurred. Antigenemia was demonstrated in all 22 patients while an antibody response occurred in 21 of them. The antigenemia assay became positive 8 +/- 7 days before the onset of symptoms while the antibody response was observed 4 +/- 9 days after the onset of symptoms. The pattern of antigenemia was helpful for monitoring the course of the infection. The maximum level of antigenemia was significantly higher and its duration significantly longer in symptomatic than asymptomatic infection. We conclude that CMV antigenemia is a sensitive, specific, and early marker of CMV infection. The antigenemia assay is of great value in monitoring patients with a high risk of CMV infection.     

Cytomegalovirus infection and graft rejection in renal transplantation

BACKGROUND: Cytomegalovirus (CMV) infection and CMV disease have been associated with acute and chronic graft rejection. The introduction of the sensitive CMV antigenemia pp65 assay for detection of CMV infection allowed us to study the time course of CMV infection and acute rejection and the long-term outcome in renal transplant recipients with and without a CMV risk constellation. METHODS: Prospective single center study including 48 renal transplant recipients at risk for CMV infection (donor and/or recipient CMV seropositive) and a control group of 36 CMV seronegative recipients of CMV seronegative kidney donors. Evidence of CMV infection was monitored by the CMV antigenemia pp65 assay every 1 to 2 weeks and compared with the occurrence of acute rejection in the posttransplant period and graft function at 5 years. RESULTS: CMV infection developed in 83% (40/48) of patients of the CMV risk group within 4 months posttransplant. A total of 18 of patients experienced an acute rejection episode (control group 16/36; P=0.65). In 12/18 CMV infection followed rejection and in three patients antigenemia preceded the diagnosis of rejection. In three patients CMV antigenemia remained negative. Five-year follow up: Patient survival (44/48 vs. 31/36; P=0.48), graft survival (38/48 vs. 27/36; P=0.79), number of patients with at least one acute rejection episode: CMV risk group: 42.1%, control group 51% (P=0.46), serum creatinine: CMV risk group:130 +/- 66 micromol/iter, control group: 126 +/- 37 micromol/ liter (P=0.56), proteinuria: CMV risk group: 0.02 +/- 0.02 g/mmol creatinine, control group: 0.02 +/- 0.02 g/mmol creatinine (P=1.0). CONCLUSION: CMV infection within 4 months posttransplant, as defined by a positive antigenemia assay was not found to be a risk factor for acute graft rejection or chronic graft dysfunction at 5 years.     

Prophylactic Therapy With Valgancyclovir in High-Risk (Cytomegalovirus D+/R−) Liver Transplant Recipients: A Single-Center Experience

A retrospective study was performed in liver transplant patients with high risk to develop cytomegalovirus infection (CMV D+/R−) who were treated with valgancyclovir for 3 months as prophylactic therapy. The aim of this study was to determine the safety and efficacy of prophylactic therapy with valgancyclovir. Weekly CMV antigenemia was routinely assessed during the first 3 months posttransplantation, twice a month to month 6, and monthly until the end of the first year, as well as when clinically indicated. The follow-up period was 1 year. From January 2003 to February 2007, 199 liver transplantations were performed at our institution, including 23 (11%) high-risk patients for CMV infection. Median age was 47 ± 11.6 years. Nineteen patients (70.4%) were men. Five subjects (21.7%) developed CMV infections. Three patients with positive CMV antigenemia at 3, 4, or 6 months posttransplantation were asymptomatic, while 2 (8.7%) showed gastrointestinal CMV disease at 2 months posttransplantation or CMV hepatitis at 1 month after the end of the prophylactic therapy. Treatment with intravenous gancyclovir followed by oral valgancyclovir was successful in both patients. No opportunistic infections were observed and only 1 patient developed leukopenia as an adverse event related to valgancyclovir.     

Cytomegalovirus-related disease and risk of acute rejection in renal transplant recipients: a cohort study with case-control analyses

The relationship between a cytomegalovirus (CMV) infection and the acute rejection of a renal transplant is not well established. The aim of the study was to document whether the clinical presentation of a CMV infection as a diffuse inflammatory disease or as a clinically asymtomatic illness is a risk factor of acute renal transplant rejection. One hundred and ninety-two consecutive renal transplant recipients were included in a historical cohort study for exposed – non exposed analyses. CMV infection after transplantation was the exposure factor. Before transplantation, 113 patients had antibodies against CMV and 79 were seronegative. The patients were divided into three groups: Group 1 consisted of 64 patients who had neither clinical signs of CMV disease nor CMV serological changes after transplantation, Group 2 consisted of 77 seropositive patients with asymptomatic viremia, and Group 3 consisted of 51 seropositive patients with clinical signs of diffuse inflammation that included fever, neutropenia, and various visceral involvements (CMV disease). Groups 2 and 3, the seropositive patients, were paired with Group 1 patients. Acute rejection was considered as CMV-induced when it occurred within one month following viremia, during the first year after transplantation. Transplant patients with CMV disease, had a significant likelihood of developing acute rejection after CMV infection or reactivation (P < 0.01). The odds ratio for developing rejection was 5.98, 95 % confidence interval: 1.21–29.40. Such a link was not documented for recipients with asymptomatic CMV infection. In conclusion, CMV disease, but not asymptomatic viremia, is a risk factor of acute renal transplant rejection. On epidemiological grounds, these results support the hypothesis that factors controlling both the viral replication and the diffuse inflammatory process are implicated in acute graft rejection. Received: 20 July 1999 Revised: 22 February 2000 Accepted: 9 June 2000     

Differences in cytomegalovirus replication quantified using quantitative polymerase chain reaction and antigenemia after allogeneic stem cell transplantation

Fifty percent of allogeneic stem cell recipients develop cytomegalovirus (CMV) infection in the first 100 days posttransplantation. Various methods have been used to determine CMV infections, including antigenemia assay and real-time polymerase chain reaction (RT-PCR). Although antigenemia assay has been used more frequently, this technique is less sensitive than RT-PCR. In contrast, RT-PCR has a low positive predictive value for CMV end-organ disease. Cytomegalovirus infections were analyzed in 41 peripheral blood samples from allogeneic stem cell recipients using both antigenemia assay and RT-PCR; results were discordant in 36.6% of patients. Although the antigenemia assay detected CMV replication in 29.2% of cases, RT-PCR was positive in 65.8%. In 83.3% of patients, results detected using the antigenemia assay were delayed by a median (range) of 5 (2-20) weeks compared with positive RT-PCR results. Within the first 100 days posttransplantation, higher levels of viral replication measured using RT-PCR were observed in patients with vs without antigenemia. In addition, in patients with antigenemia, viral load was significantly higher before day 100 than after (P=.01 and P=.008, respectively) compared with those without antigenemia.     

Cytomegalovirus infection with multiple colonic perforations in a renal transplant recipient

Cytomegalovirus (CMV) continues to be potentially the most important pathogen affecting organ transplant recipients. Severe gastrointestinal complications have been reported to occur in about 10% of renal transplant recipients, sometimes with dramatic presentations. We report the case of a 57-year-old CMV-seropositive woman with end-stage renal failure who developed CMV-related colonic multiple perforation 30 days after cadaveric CMV-positive renal transplantation. CMV pp65 antigenemia test and CMV-PCR had always been negative on all the weekly controls routinely performed in the postoperative period. Only after the sudden onset of this complication did the antigenemia and PCR become positive. The relationship between infection and perforation has been established beyond any doubt, as the histology of the resected colonic segment revealed florid CMV infection with evidence of typical inclusions in both macrophages and endothelial cells. Colonic perforations are often fatal in transplant recipients because of inability to contain the perforation, and only a rapid diagnosis and an aggressive surgical treatment can improve the prognosis.     

An assessment of interactions between hepatitis C virus and herpesvirus reactivation in liver transplant recipients using molecular surveillance.

Hepatitis C virus (HCV) has been proposed to have immunomodulatory effects in transplant recipients and may promote herpesvirus reactivation. To assess this, we compared the incidence of herpesvirus reactivation in HCV-positive and HCV-negative liver transplant recipients. Quantitative viral load testing was performed at regular intervals posttransplantation for cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesviruses (HHV) 6, 7, and 8, and varicella zoster virus (VZV) in 177 liver transplant patients who were HCV-positive (n=60) or HCV-negative (n=117). The incidence of CMV disease, CMV viremia, and the peak CMV viral load was not significantly different in HCV-positive vs. HCV-negative patients. Similarly, no differences in HHV-6 or EBV reactivation were observed. HHV-8 or VZV viremia was not detected in any patient in the study. A lower incidence of HHV-7 infection occurred in HCV-positive patients vs. HCV-negative patients (47.6% vs. 72.7%; P=0.006). In conclusion, these results suggest that HCV infection does not appear to promote herpesvirus reactivation after liver transplantation.     

Late-onset cytomegalovirus reactivation in critically ill renal transplant patients

BACKGROUND: Cytomegalovirus (CMV) reactivation occurs frequently in the first months after renal transplantation. However, reports concerning long-term kidney transplant recipients are rare and have always pertained to symptomatic CMV disease. METHODS: We report four cases of late-onset asymptomatic CMV reactivation in critically ill renal transplant patients who suffered from severe bacterial infections and in whom CMV antigenemia was observed. RESULTS AND CONCLUSION: CMV reactivation in these patients might indicate an additional disturbance in the patients' immune defenses at the time of critical illness, possibly even necessitating a temporary reduction in immunosuppressive therapy. Prospective, controlled trials are needed to define the role of CMV antigenemia in critically ill patients, including the role of antiviral therapy for asymptomatic reactivations.