A prospective analysis interstitial pneumonia and opportunistic viral infection among recipients of allogeneic bone marrow grafts.

A prospective study of 80 bone marrow transplant recipients with acute leukemia and aplastic anemia employed serial viral cultures, determination of complement-fixing antibody to cytomegalovirus (CMV), and study of material obtained from open lung biopsy and autopsy. There were 43 episodes of interstitial pneumonia, 28 of which were fatal. About 40% of the cases were idiopathic. CMV was the most common candidate pathogen, present in 47% of affected lungs. By a median of 53 days following transplantation, 46% of the recipients were shedding CMV from some site. This event was three times more frequent among recipients who had positive titers of antibody to CMV before transplantation than among seronegative recipients. Failure to respond werologically to CMV infection markedly increased the hazard of dying of interstitial pneumonia. Graft-vs-host disease significantly increased the incidence and lethality of interstitial pneumonia. The presence of leukemia (rather than aplastic anemia) and/or certain factors in the technique of preparation for engraftment may have been significant.     

Thrombotic microangiopathy and cytomegalovirus in liver transplant recipients: a case-based review

Background. Thrombotic microangiopathy (TMA) is a rare but potentially lethal complication encountered in solid organ and bone marrow transplant recipients, requiring rapid recognition, diagnosis, and initiation of therapy. Several potential causes have been identified in this setting, including viral infections and medications. Methods. We report a case of TMA in a liver transplant recipient with active cytomegalovirus (CMV) gastritis. A 41‐year‐old female presented 3 months after liver transplantation with a 5‐week history of nausea, vomiting, anorexia, and diarrhea. CMV serology was donor seropositive and recipient seronegative (D+/R?). The immunosuppressive regimen consisted of tacrolimus, mycophenolate mofetil, and prednisone. Evaluation revealed CMV viremia with a high viral load and intravenous ganciclovir was started. A decline in hemoglobin and platelets with an increase in lactate dehydrogenase (LDH) warranted hematologic evaluation, which revealed findings consistent with microangiopathic hemolytic anemia. Ganciclovir and tacrolimus were discontinued. Intravenous immunoglobulin was administered and daily plasmapheresis was initiated. As the patient's blood counts and LDH started to improve, ganciclovir was cautiously reinstituted. The patient's gastrointestinal symptoms gradually resolved and her blood counts continued to improve with prolonged plasmapheresis (a total of 23 plasmapheresis sessions). Tacrolimus and possibly CMV infection were suspected to be the cause for her TMA, and cyclosporine was substituted. Conclusions. TMA is an important entity in the differential diagnosis of acute hemolytic anemia in liver transplant recipients. Many cases seem to be medication‐induced. However, in treatment‐resistant or relapsing cases, a possibility of concomitant CMV infection should be considered.     

Early infections in adults undergoing matched related and matched unrelated/mismatched donor stem cell transplantation: a comparison of incidence

We compared the incidence of early infectious complications between matched related (MR) and matched unrelated/mismatched (MU/MM) allogeneic stem cell transplant (allo-SCT) recipients in a single centre over a 6-year period in 214 consecutive adult patients. Early infections were defined as occurring from hospital admission for SCT until discharge. One hundred and fifty-nine patients received an allograft from MR donors and 55 patients received MU/MM allo-SCT. One hundred and eight of 214 patients had 147 episodes of fever. Ninety-three episodes (63%) were due to clinically or microbiologically documented infections and 54 episodes (37%) to fever not related to infection. Patients undergoing MU/MM transplantation tended to have more documented infections compared to recipients of MR allo-SCT (P = 0.06). Significantly more MU/MM transplant recipients had breakthrough infections with Herpes simplex virus type 1 (HSV-1, P = 0.003), and more CMV reactivation (P = 0.015). The mortality rate in all patients during hospitalisation post-SCT was 6.3% in MR and 18.2% in MU/MM allo-SCT recipients (P = 0.009). Early mortality was associated with infection in 70% of the patients, with a similar distribution between MR and MU/MM transplant recipients. However, MU/MM transplant recipients had significantly more early deaths due to toxic causes (P < 0.001). We conclude that early post-transplant MU/MM transplant recipients tend to have more documented infections, and have significantly more breakthrough infections with HSV-1 and more CMV reactivation. MU/MM transplant recipients are at higher risk of early mortality, especially due to toxic causes.     

Cryptosporidium parvum-associated sclerosing cholangitis in a liver transplant patient

Abstract: Cryptosporidium parvum causes severe long-standing diarrhea in immunocompromised patients. Sclerosing cholangitis caused by C. parvum is a rare complication in transplant recipients. We report herein the presentation of Cryptosporidium -associated cholangitis in an adult liver transplant patient diagnosed by liver biopsy. The patient improved on treatment with azithromycin and paromomycin.     

The rapid diagnosis of pulmonary infections in solid organ transplant recipients

A rapid diagnostic team was formed to facilitate the diagnosis of pulmonary infections in solid organ transplant recipients. Seventy-seven renal and three liver transplant recipients developed 86 episodes of pneumonitis between 6 and 2,410 days posttransplant (median, 117 days). A diagnosis was established in all but seven patients. More than one diagnosis was established in 25. Cytomegalovirus (CMV) occurred in 51 episodes, bacterial pneumonia in 16 episodes, Pneumocystis carinii (PCP) in 11 episodes, fungal or Nocardia in 10 episodes, and Legionellosis in six episodes. Over half of the episodes of pneumonitis occurred in the period 1 to 4 months posttransplant. Bacterial pneumonia occurred significantly later than pneumonitis caused by PCP, Legionella, or CMV. Death occurred in 24 transplant recipients (31%) including 19 of 49 patients (39%) with CMV. Diffuse disease was the most common abnormality noted on initial chest roentgenogram (79 of 111, 71%). Interstitial infiltrates were the most common type of radiographic lesion observed, accounting for 62 of 111 (56%). Fiberoptic bronchoscopy was performed in 69 transplant recipients. Thirty-six of the 65 diagnoses made were established early, within 24 hours after bronchoscopy. Of the remaining diagnoses established later than 24 hours, all but one case of CMV was included. Bronchial alveolar lavage alone established 31 of the diagnoses. Bronchial brushings alone established only six cases, including five episodes of bacterial pneumonia and one case of CMV. We conclude that a team approach relying on fiberoptic bronchoscopy is useful in establishing the diagnosis of pulmonary infections in solid organ transplant recipients.     

Low incidence of transplant coronary artery disease in Chinese heart recipients.

OBJECTIVES: This study sought to assess the incidence of transplant coronary artery disease (CAD) in Chinese heart recipients. BACKGROUND: The prevalence of transplant CAD detected by angiography at 1, 2 and 4 years after heart transplantation was 11%, 22% and 45%, respectively. The incidence of transplant CAD in Chinese heart recipients has not been reported. METHODS: For those recipients surviving for more than 1 year after transplantation, coronary angiography was performed annually for surveillance of transplant CAD. The recipient characteristics, donor characteristics, rejection episodes, medication and human leukocyte antigen (HLA) mismatches were recorded. RESULTS: Fifty patients were included in this study. Thirteen (26%) recipients had ischemic heart disease. Two patients (4%) had active cytomegalovirus (CMV) infection after transplantation. The mean number of rejection episodes in the 1st year after transplantation was 1.15. Among 47 patients with complete data of donor and recipient histocompatibility antigens, there were seven patients (14.9%) with two or fewer HLA mismatches. Among 74 angiograms of 50 patients reviewed, only one patient had discrete stenosis less than 50% in the middle portion of the left anterior descending artery at 1 year after transplantation. The cumulative incidence of transplant CAD was 2% at 1 year and 2% at 2 and 4 years after transplantation. CONCLUSIONS: The incidence of transplant CAD was low in Chinese heart transplant recipients. Low percentage of ischemic heart disease in recipients, low occurrence of active CMV infection and rejection episodes after transplantation, less racial disparity, and lower HLA mismatches may be the important factors.     

Evaluation of viral load and antigenemia as markers for relapse cytomegalovirus infection in renal transplant recipients

Cytomegalovirus (CMV) is a pathogen, commonly found in the donors and recipients of solid organ transplantation. CMV is one of the major causes of morbidity and mortality in these patients. Relapsing episodes of CMV infection occur in 23-33% of transplant patients which is likely a reflection of incomplete suppression of viral replication following antiviral treatment with intravenous ganciclovir. We have studied CMV DNA load and antigenemia as markers for relapse of CMV infection in 49 renal transplant patients out of 68 with CMV infection who received a course of intravenous ganciclovir among 300 transplants carried out between January of 2001 and June of 2005. Viral load and antigenemia were measured in blood samples obtained before, during and at the completion of treatment. We also studied different viral load as predictors of relapse CMV infection. Twelve (24.5%) of 49 recipients developed relapsing CMV infection. The relapsing group had higher viral loads after treatment than the no relapsing group. There was no difference in antigenemia level between both groups. The viral loads before and during the treatment, the age and sex of donors and recipients, inmunosupresión, percentage of seronegative recipients with seropositive donors, duration of the therapy and the percentage of patients with heavy immunosuppression were similar in the two groups, but the incidence of acute rejection was higher in the relapsing group. We also evaluated the range of viral load after treatment which is able to trigger the relapse of CMV infection. We conclude that CMV DNA load after treatment is a useful marker for individualizing antiviral treatment of CMV infection in renal transplant recipients. Acute rejection is a risk factor to the relapsing CMV infection.     

Infectious complications after kidney transplantation: a single-center experience

Infectious complications after renal transplantation are associated with significant morbidity and mortality. The prevalence of infections in transplant recipients varies from country to country. This study sought to assess the overall incidence of post-transplant infectious complications at our research center in Iran, compared with other centers in the world. Between 2002 and 2004, 179 renal transplantations were performed in our center. Of these, 142 were studied and followed for 1 year. Immunosuppressive regimens were cyclosporine, mycophenolate mofetil, and prednisolone. The overall incidence of infections was 54.2%. The most common sites of infections were the urinary tract (41.5%) and the respiratory tract (6.3%). The most frequent causes of infections were Klebsiella (24%) and cytomegalovirus (CMV) (17.6%). Wound infection occurred in 4.9% of the patients. Three (2.1%) patients developed hepatitis C and 2 (1.4%) had mycobacterial infections. There was no case of Pneumocystis pneumonia. Overall mortality was 7.7%. Infection-related mortality was 3.5%. In conclusion, this study identifies infections as the cause of morbidity and mortality in the post-transplant period. There was a low incidence of tuberculosis (<2% yearly) and a high incidence of CMV disease in our recipients.     

Diversity of antiviral‐resistant human cytomegalovirus in heart and lung transplant recipients

J.M. Iwasenko, G.M. Scott, Z. Naing, A.R. Glanville, W.D. Rawlinson. Diversity of antiviral‐resistant human cytomegalovirus in heart and lung transplant recipients.
Transpl Infect Dis 2011: 13: 145–153. All rights reserved Abstract: Immunocompromised transplant recipients are at high risk for human cytomegalovirus (CMV)‐related infection and disease. Antiviral prophylaxis and treatment have reduced CMV morbidity and mortality, but at times promote development of antiviral‐resistant CMV strains that can significantly contribute to adverse clinical outcomes in transplant recipients. We have investigated CMV genotypes in transplant recipients (bone marrow, stem cell, kidney, heart, lung, and liver) receiving antiviral prophylaxis or preemptive therapy or treatment, to determine the viral characteristics and clinical impact of antiviral‐resistant CMV in these different groups. Antiviral‐resistant CMV strains were detected by polymerase chain reaction sequencing of the CMV protein kinase (UL97) and viral DNA polymerase (UL54) genes from clinical specimens. A trend toward more frequent detection of multidrug resistance and co‐circulation of multiple resistant strains was seen in heart and lung transplant recipients compared with other transplantation types. A greater diversity and number of UL97 and UL54 mutations were observed in heart and lung transplant recipients; whereas antiviral‐resistant CMV infections in other transplant recipients were predominantly the result of a single mutant genotype. Furthermore, 43% (6/14) of CMV‐positive heart and lung transplant recipients were infected with CMV strains containing UL54 mutations conferring multidrug resistance compared with only 6% (1/18) of CMV‐positive recipients of other transplanted organs or stem cells. Emergence of CMV strains containing previously unrecognized UL54 mutations (F412S and D485N) also occurred in 1 lung and 1 heart transplant recipient. The development of these mutations under antiviral selective pressure, and clinical outcome of infection suggests these mutations are likely to confer antiviral resistance. Emergence of CMV antiviral resistance remains a significant issue in immunocompromised patients treated with antiviral agents, and emphasizes the relevance of regular antiviral resistance testing when designing optimal patient‐management strategies.     

Lower incidence of cytomegalovirus infection with everolimus versus mycophenolate mofetil in de novo cardiac transplant recipients: a randomized, multicenter study

M. Viganò, T. Dengler, M.F. Mattei, A. Poncelet, J. Vanhaecke, E. Vermes, R. Kleinloog, Y. Li, Y. Gezahegen, J.F. Delgado, on behalf of the RAD A2411 Study Investigators. Lower incidence of cytomegalovirus infection with everolimus versus mycophenolate mofetil in de novo cardiac transplant recipients: a randomized, multicenter study.
Transpl Infect Dis 2010: 12: 23–30. All rights reserved
Abstract: Cytomegalovirus (CMV) is a major cause of infectious complications following cardiac transplantation, severely affecting short- and long-term outcomes. A 12-month, multicenter, randomized, open-label study in de novo cardiac transplant patients was undertaken to compare the efficacy, renal function, and safety of everolimus plus reduced cyclosporine versus mycophenolate mofetil (MMF) plus standard cyclosporine (ClinicalTrials.gov NCT00150046). CMV-specific data was prospectively collected on infections, laboratory evidence, CMV syndrome, and CMV disease. In total, 176 patients were randomized (everolimus 92; MMF 84). Use of CMV prophylaxis was similar between groups (everolimus 20.8%; MMF 24.0%). Patients in the everolimus arm had a significantly lower incidence of any CMV event (8.8% versus 32.5% with MMF, P <0.001), CMV infection as an adverse event (4.4% versus 16.9%, P =0.011), laboratory evidence of CMV (antigenemia 7.7% versus 27.7%, P <0.001; polymerase chain reaction assay 2.2% versus 12.0%, P =0.015), and CMV syndrome (1.1% versus 8.4%, P =0.028). In the donor (D)+/recipient (R)+and D−/R+ subgroups, even after adjusting for use of prophylaxis, the CMV event rate remained significantly lower with everolimus than with MMF ( P =0.0015 and P =0.0381, respectively). In conclusion, de novo cardiac transplant recipients experienced lower rates of CMV infection, CMV syndrome, or organ involvement on an everolimus-based immunosuppressant regimen compared with MMF.     

Cytomegalovirus pneumonia in adult autologous blood and marrow transplant recipients

CMV pneumonia is a major cause of morbidity and mortality among allogeneic BMT recipients. To assess the frequency, timing, risk factors and response to therapy of CMV pneumonia among autologous BMT recipients, we reviewed our experience with 795 patients. Sixteen (2%) patients were diagnosed with CMV pneumonia. The frequency was higher among patients who were seropositive than those who were seronegative (3.3% vs 0%, P = 0.008). Among seropositive patients, the frequency was higher among patients with hematological malignancies than patients with solid tumors (5.0 % vs 1.0%, P = 0.019). Eleven cases occurred <30 days, and five cases occurred >100 days post transplant. The overall CMV pneumonia-related mortality rate was 31%. Seven (78%) of nine patients treated with ganciclovir and IVIG prior to respiratory failure survived; neither of two patients treated after respiratory failure survived. Four of five (80%) untreated patients survived. In conclusion, CMV is a not infrequent cause of pneumonia among autologous BMT recipients. Risk factors include CMV seropositivity and an underlying hematological malignancy. A favorable response hinges on the prompt initiation of therapy. The survival of 25% of the patients without antiviral therapy suggests that the isolation of CMV from a BAL specimen occasionally reflects oropharyngeal contamination or that CMV pneumonia may sometimes be self-limited in more immunocompetent autologous BMT recipients.     

Fever in renal transplant recipients: causes, prognostic significance and changing patterns at the University of Minnesota Hospital

During a three year period in which 433 renal transplants were performed, 194 episodes of fever were documented in allograft recipients hospitalized at the University of Minnesota. Viral infections were responsible for over half of the febrile episodes, and 98 (51 percent) of the fevers were associated with cytomegalovirus (CMV), either occurring alone or in conjunction with allograft rejection or another systemic infection. Bacterial infections, fungal infections and rejection were other important causes of fever, accounting for 14 percent, 5 percent and 13 percent of the febrile episodes, respectively. Most fevers occurred in the first four months after transplantation; although about two thirds of these fevers were due to CMV, only 17 percent of fevers that occurred more than one year after the renal transplant were due to CMV. Bacterial and fungal infections and malignancy were important causes of these fevers. Of the febrile illnesses associated with transplant nephrectomy or death, a majority occurred in patients with CMV disease. Secondary bacterial and/or fungal infections were observed in a large majority of patients with lethal CMV disease. During the third year of this study there was a significant decrease in the proportion of febrile episodes due to CMV.     

Clinical trial of quantitative real-time polymerase chain reaction for detection of cytomegalovirus in peripheral blood of allogeneic hematopoietic stem-cell transplant recipients

The preemptive therapy of cytomegalovirus (CMV) reactivation is useful for the prevention of CMV disease in allogeneic hematopoietic stem-cell transplant (HSCT) recipients. We compared results of the pp65 CMV antigenemia test with quantitative touch-down polymerase chain reaction (Q-PCR) on unfractionated whole blood for the detection of CMV reactivation in 51 HSCT recipients. Forty episodes of reactivation in 28 patients were detected by antigenemia and treated by antiviral drugs. Q-PCR detected CMV DNA in 39 (97.5%) of 40 reactivation episodes. False-positive results occurred in 3% of tests, of which 63% were borderline positive. Q-PCR results were positive earlier than antigenemia results in 30 (77%) of 39 episodes detected by antigenemia. Q-PCR remained positive after treatment was discontinued in 14 (36%) of 39 episodes and predicted the return of CMV reactivation in 4 (31%) of 13 episodes. Q-PCR was more sensitive than the antigenemia test and had sufficient specificity for clinical use.     

Diagnostic yield of bronchoalveolar lavage following renal transplantation

Abstract: Organ transplant recipients are at high risk of infectious pulmonary complications. In this retrospective study, the diagnostic yield of bronchoalveolar lavage (BAL) was evaluated in renal transplant recipients. The results were analysed in special regard to the clinical presentation of pulmonary infections and the possible impact of new immunosuppressive agents. Over a 5‐year period 91 BAL were performed in 71 renal transplant recipients. Microorganisms were isolated from 69% of BAL (63/91): bacteria 32%; cytomegalovirus (CMV) 27%; Pneumocystis carinii (PC) 22%; other viruses 9% (HSV; EBV, RSV, adenovirus, HHV8); Aspergillus fumigatus 1%. Total cell counts and neutrophil counts in BAL were significantly elevated in bacterial infection, whereas BAL positive for PC showed eosinophilia (P<0.05). There was no association between clinical symptoms and the radiological pattern of infiltrates and the type of infection. Immunosuppression containing tacrolimus or mycophenolate mofetil was associated with a significantly higher percentage of PC and CMV infections compared to cyclosporin‐based immunosuppression (65% vs. 30%, P<0.005). A considerable number of PC and CMV infections occurred beyond 6 months after transplantation. In conclusion, BAL has a high diagnostic yield in renal transplant recipients. Infection with CMV and PC should also be considered beyond 6 months after transplantation, and prophylaxis for opportunistic infections should be given if the immunosuppression is intensified.     

Unusual presentation of cytomegalovirus enteritis after liver and kidney transplantation

Cytomegalovirus (CMV) is a cause of significant morbidity and mortality in solid organ transplant recipients. Gastrointestinal (GI) tract infection by CMV in this population can cause symptomatic disease, which typically manifests as fever, abdominal pain, nausea, and bloody diarrhea. Erosive lesions of the GI mucosa are often evident on endoscopic exam. We report an unusual presentation of CMV enteritis in a kidney and liver transplant recipient with the development of acute onset voluminous watery diarrhea in the absence of other typical symptoms and subsequent progression to hypovolemic shock and acute renal failure. This case emphasizes the atypical presentations of common opportunistic infections that may occur in immunosuppressed hosts.     

Late cytomegalovirus pneumonia in adult allogeneic blood and marrow transplant recipients.

To assess the impact of antiviral prophylaxis during the first 3 months after transplantation on the frequency, timing, and outcome of cytomegalovirus (CMV) pneumonia during the first year, 541 adult allogeneic blood and marrow transplant recipients were evaluated. Thirty-four patients (6.3%) developed 35 episodes of CMV pneumonia at a mean of 188 days after transplantation, with an associated mortality rate of 76%. Twenty-six episodes (74%) occurred late (after day 100). Of the patients with late CMV pneumonia almost all (92%) had chronic graft vs. host disease or had received T cell-depleted transplants. Fourteen late CMV pneumonias (54%) were associated with serious concurrent infections, and 100% of these episodes were fatal. In conclusion, although the frequency of CMV pneumonia in the early posttransplantation period may be substantially reduced by prophylaxis, CMV continues to be a major cause of morbidity and mortality in the late period. Some subsets of patients need more prolonged surveillance and prophylaxis and/or preemptive therapy.     

Quantification of cytomegalovirus DNA in BAL fluid: a longitudinal study in lung transplant recipients

STUDY OBJECTIVES: Cytomegalovirus (CMV) infection is common in patients receiving solid organ transplants, and it is associated with increased morbidity as well as risk for development of chronic rejection. A rapid and sensitive diagnostic method would improve the therapeutic management of CMV infection, including the monitoring of treatment effects. We investigated whether longitudinal determinations of CMV DNA quantities in BAL fluid could be useful for this purpose. DESIGN: CMV DNA levels in 340 BAL samples from 35 consecutive lung transplant recipients were studied during a median of 18 months. Seventeen (49%) of the patients developed CMV disease with pneumonitis. Twenty-seven CMV disease episodes were diagnosed. RESULTS: Patients with CMV disease had a significantly higher mean level of CMV copies per milliliter BAL fluid (1,120 +/- 4,379) compared with those without (180 +/- 1,177, p < 0.01). Viral load as well as acute rejection requiring treatment (>/= A2) were independent risk factors associated with CMV disease. Differences between the groups concerning HLA-DR matching, basic immunosuppressive therapy, and CMV serologic status D/R -/+ vs D/R +/+ were not significant. A diagnostic definition of normality based on the mean level of all episodes without CMV disease +2 SD would discriminate only 9 of the 27 CMV episodes. CONCLUSIONS: Although the viral load is increased during episodes of clinical CMV disease in lung transplant recipients, the quantitative PCR assessment of CMV DNA in BAL fluid is not discriminative enough to be useful as a diagnostic tool for CMV disease.     

Preemptive treatment approach to cytomegalovirus (CMV) infection in solid organ transplant patients: relationship between compliance with the guidelines and prevention of CMV morbidity

Cytomegalovirus (CMV) remains a major cause of morbidity in solid organ transplant patients. In order to reduce CMV morbidity, we designed a program of routine virological monitoring that included throat and urine CMV shell vial culture, along with peripheral blood leukocyte (PBL) shell vial quantitative culture for 12 weeks post‐transplantation, as well as 8 weeks after treatment for acute rejection. The program also included preemptive ganciclovir treatment for those patients with the highest risk of developing CMV disease, i.e., with either high‐level viremia (>10 infectious units [IU]/10⁶ PBL) or low‐level viremia (<10 IU/10⁶ PBL) and either D+/R? CMV serostatus or treatment for graft rejection. During 1995–96, 90 solid organ transplant recipients (39 kidneys, 28 livers, and 23 hearts) were followed up. A total of 60 CMV infection episodes occurred in 45 patients. Seventeen episodes were symptomatic. Of 26 episodes managed according to the program, only 4 presented with CMV disease and none died. No patient treated preemptively for asymptomatic infection developed disease. In contrast, among 21 episodes managed in non‐compliance with the program (i.e., the monitoring was not performed or preemptive treatment was not initiated despite a high risk of developing CMV disease), 12 episodes turned into symptomatic infection (P=0.0048 compared to patients treated preemptively), and 2 deaths possibly related to CMV were recorded. This difference could not be explained by an increased proportion of D+/R? patients or an increased incidence of rejection among patients with episodes treated in non‐compliance with the program. Our data identify compliance with guidelines as an important factor in effectively reducing CMV morbidity through preemptive treatment, and suggest that the complexity of the preemptive approach may represent an important obstacle to the successful prevention of CMV morbidity by this approach in the regular healthcare setting.     

Oral ganciclovir versus valganciclovir for cytomegalovirus prophylaxis in high-risk liver transplant recipients

Abstract: This retrospective review compared oral valganciclovir (VGCV) 450 mg daily for 6 months versus oral ganciclovir (GCV) 1000 mg 3 times daily for 3 months in preventing cytomegalovirus (CMV) disease in high-risk liver transplant recipients. We evaluated all CMV donor positive–recipient negative liver transplant recipients managed at University Health System in San Antonio, Texas from August 1996 to September 2006. CMV disease was confirmed by polymerase chain-reaction or antigenemia assay, and CMV invasive disease by tissue biopsy. Patient demographics, laboratory results, complications, and therapies were collected via retrospective chart review. Patients <18 years of age or those who died during transplant admission were excluded. Primary endpoints included incidence, onset, and severity of CMV disease up to 1 year post transplant. Data collection also included patient demographics, immunosuppression, CMV treatment regimens, and relevant lab results. A total of 64 patients (43 VGCV and 21 GCV) were identified. Four patients developed CMV disease: VGCV (3/43, 7%) versus GCV (1/21, 5%) ( P =1.0), with 1 VGCV patient experiencing tissue-invasive CMV. In all cases, onset of CMV disease occurred after prophylaxis was discontinued. Onset occurred at 24, 27, and 45 weeks post transplant in the VGCV group, and at 26 weeks in the 1 patient on GCV. Four patients received rabbit anti-thymocyte globulin (rATG) induction; 1 patient received rATG and developed CMV disease, with no statistical difference compared with the 3 remaining patients who received rATG but did not develop CMV disease ( P =0.09). No difference was found in incidence of CMV disease between patients who received GCV and those who received VGCV at our institution.     

Human herpesvirus 6 infection of the gastroduodenal mucosa.

BACKGROUND: Human herpesvirus 6 (HHV-6) infections are usually asymptomatic reactivations in adult liver transplant recipients, but they may also cause fever or graft dysfunction. HHV-6 infection can also present symptoms of gastroenteritis. In this study, we investigated the presence of HHV-6 in the gastroduodenal mucosa of liver transplant recipients and in immunocompetent patients undergoing gastroscopic examination because of dyspeptic symptoms. METHODS: HHV-6 and cytomegalovirus (CMV) examinations were performed on gastroduodenal biopsy specimens obtained during upper gastrointestinal endoscopic examinations from 90 liver transplant recipients and from 31 immunocompetent patients with upper gastrointestinal symptoms. In the gastroduodenal mucosa, HHV-6 and CMV was demonstrated by immunohistochemistry in frozen sections using monoclonal antibodies against HHV-6- and CMV-specific antigens. RESULTS: HHV-6-positive cells were found in biopsy specimens from 21 (23%) of the liver transplant recipients and 6 (19%) of the immunocompetent patients, CMV-positive cells were found in specimens from 55 (61%) of the transplant recipients and 7 (23%) of the immunocompetent patients, and 12 transplant recipients were found to have both HHV-6 and CMV infection. Fifteen transplant recipients with positive HHV-6 findings in the gastroduodenal mucosa also had HHV-6 antigenemia, whereas 30 patients with HHV-6 antigenemia did not have gastroduodenal involvement. Endoscopic findings in these patients included biliary complications in 10 patients and gastritis in 2 patients. Histopathological findings were nonspecific and included very mild inflammation. A total of 30 (94%) of the transplant recipients with biliary complications also had HHV-6 or CMV detected in the duodenal mucosa. CONCLUSIONS: HHV-6-positive cells and CMV-positive cells were frequently found in the gastroduodenal mucosa of liver transplant recipients and of immunocompetent patients undergoing gastroscopic examination because of dyspeptic symptoms.