Cytomegalovirus Infection Status Research Articles

Assigning Cytomegalovirus Status in Children Awaiting Organ Transplant: Viral Shedding, CMV-Specific T Cells, and CD27-CD28-CD4+ T Cells.

Passive antibodies, maternal or transfusion-acquired, make serologic determination of pretransplant cytomegalovirus (CMV) status unreliable. We evaluated 3 assays unaffected by passive antibodies, in assignment of CMV infection status in children awaiting solid organ transplant and in controls: (1) CMV nucleic acid amplification testing (NAAT), (2) quantification of CMV-specific CD4+ T cells, and (3) quantification of CD27-CD28-CD4+ T cells. Our results highlight that CMV NAAT, from urine and oropharynx, is useful in confirming positive CMV status. Detection of CMV-specific CD4+ T cells was sensitive and specific in children >18 months but was less sensitive in children <12 months. CD27-CD28-CD4+ T cells are not likely useful in CMV risk stratification in children.

Assignment of cytomegalovirus infection status in infants awaiting solid organ transplant: Viral detection methods as adjuncts to serology.

Assignment of CMV infection status in infants awaiting SOT is challenging as passive maternal antibody can lead to false-positive serology. Since 2000, our protocol has recommended sending throat and urine samples for CMV viral detection, culture, or NAAT, for CMV-seropositive infants <18months awaiting SOT. We reviewed pretransplant CMV serology for 152 infants and, for CMV seropositives, examined relationships between CMV IgG OD values, age, and CMV viral detection to explore time to clearance of maternal CMV IgG and evaluate viral detection in assignment of pretransplant CMV infection status. The proportion of CMV-seropositive infants decreased from 52% in infants 0-6months of age to 28% in those 12-18months. Among CMV-seropositive infants, median OD was significantly higher in the 6- to 12- and 12- to 18-month groups compared to the 0- to 6-month group. Distribution of OD by age group suggested that maternal antibody cleared before 12months. Of 59 eligible CMV-seropositive infants, 49 (83%) had CMV viral detection studies and 18 of 49 (36.7%) had detectable CMV: 9 of 30 (30.0%) infants 0-6months, 7 of 15 (46.7%) infants 6-12months, and 2 of 4 (50.0%) infants 12-18months. CMV viral detection studies are useful to confirm positive CMV infection status in CMV-seropositive infants awaiting SOT. Maternal CMV IgG likely clears before 12months.

Outcomes and prognostic factors of non-HIV patients with pneumocystis jirovecii pneumonia and pulmonary CMV co-infection: A Retrospective Cohort Study

BackgroundPneumocystis jirovecii pneumonia (PJP) and pulmonary cytomegalovirus (CMV) infection are common opportunistic infections among immunocompromised patients. However, few studies have evaluated their co-infection, especially among non-HIV patients. Therefore, we aimed to evaluate the outcomes and prognostic factors among non-HIV patients with PJP according to their CMV infection status.MethodsThis retrospective study evaluated non-HIV patients who were diagnosed with PJP between January 2009 and January2016.The patients were classified and compared according to their pulmonary CMV infection status (positive infection: bronchoalveolar lavage fluid [BALF] CMV DNA loads of >500copies/mL).ResultsAmong 70 non-HIV patients with PJP, we identified 38 patients (54.3%) with pulmonary CMV infection. There was no significant difference in the mortality rates for the two groups (p = 0.15). Pulmonary CMV infection was significantly more common among patients who were receiving glucocorticoids and immunosuppressants, compared to corticosteroids only (p = 0.02). Pulmonary CMV infection was also significantly associated with severe dyspnea, a lower PaO2/FiO2, and the presence of centrilobular nodules (p = 0.008). Higher CMV DNA loads in the BALF were positively associated with mortality (p = 0.012).ConclusionsCombined therapy using corticosteroids and other immunosuppressants may be a risk factor for pulmonary CMV co-infection among patients with PJP. In addition, CMV pneumonia should be considered when centrilobular nodules and/or severe hypoxemia are observed in non-HIV patients with PJP. Furthermore, antiviral treatment should be promptly initiated for patients with a high CMV DNA load in BALF, based on their poor prognosis.

Vascularized composite allotransplantation: current standards and novel approaches to prevent acute rejection and chronic allograft deterioration.

The advent of more potent immunosuppressants led to the first successful human upper extremity transplantation in 1998. At this time, >100 upper extremity transplants, 30 face transplants, and a variety of other vascularized composite allotransplantation (VCA) procedures have been performed around the world. VCA recipients present unique challenges for transplantation. The incidence of acute rejection exceeds 80% in hand and face transplantation and is well documented, whereas reports about antibody-mediated rejection and chronic rejection remain scarce. Immunosuppression protocols commonly used at US centers are derived from solid organ transplantation protocols. Novel approaches to minimize rejections in VCA may include improved HLA matching and considerations toward cytomegalovirus infection status. New graft preservation techniques may decrease immunogenicity prior to transplant. Novel monitoring methods such as valid biomarkers, ultrasound biomicroscopy, and sentinel flaps may enable earlier diagnosis of rejection. Cell-based therapies are being explored to achieve immunosuppressive regimen minimization or even tolerance induction. The efficacy of local immunosuppression in clinical VCA remains controversial. In conclusion, although immunosuppressive strategies adapted from SOT have demonstrated good midterm results, focusing on the unique features of VCA grafts may enable additional, more specific treatment strategies in the future and improved long-term graft outcomes.

Elevated HbA(1c) levels and the accumulation of differentiated T cells in CMV(+) individuals.

Aims/hypothesisBiological ageing of the immune system, or immunosenescence, predicts poor health and increased mortality. A hallmark of immunosenescence is the accumulation of differentiated cytotoxic T cells (CD27−CD45RA+/−; or dCTLs), partially driven by infection with the cytomegalovirus (CMV). Immune impairments reminiscent of immunosenescence are also observed in hyperglycaemia, and in vitro studies have illustrated mechanisms by which elevated glucose can lead to increased dCTLs. This study explored associations between glucose dysregulation and markers of immunosenescence in CMV+ and CMV− individuals.MethodsA cross-sectional sample of participants from an occupational cohort study (n = 1,103, mean age 40 years, 88% male) were assessed for HbA1c and fasting glucose levels, diabetes, cardiovascular risk factors (e.g. lipids), numbers of circulating effector memory (EM; CD27−CD45RA−) and CD45RA re-expressing effector memory (EMRA; CD27−CD45RA+) T cells, and CMV infection status. Self-report and physical examination assessed anthropometric, sociodemographic and lifestyle factors.ResultsAmong CMV+ individuals (n = 400), elevated HbA1c was associated with increased numbers of EM (B = 2.75, p < 0.01) and EMRA (B = 2.90, p < 0.01) T cells, which was robust to adjustment for age, sex, sociodemographic variables and lifestyle factors. Elevated EM T cells were also positively associated with total cholesterol (B = 0.04, p < 0.05) after applying similar adjustments. No associations were observed in CMV− individuals.Conclusions/interpretationThe present study identified consistent associations of unfavourable glucose and lipid profiles with accumulation of dCTLs in CMV+ individuals. These results provide evidence that the impact of metabolic risk factors on immunity and health can be co-determined by infectious factors, and provide a novel pathway linking metabolic risk factors with accelerated immunosenescence.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-015-3731-4) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

A clinical significance of assessing cytomegalovirus infection status in patients with ulcerative colitis.

A clinical significance of assessing cytomegalovirus infection status in patients with ulcerative colitis.

Immune resilience in HIV-infected individuals seronegative for cytomegalovirus.

Low CD4/CD8 T-cell ratios occur in conditions associated with reduced immune resilience, including older age and HIV infection. Effective antiretroviral therapy increases CD4/CD8 T-cell ratios, but often not to preinfection levels. The reasons for this deficit remain unclear. As cytomegalovirus (CMV) infection exacerbates falling CD4/CD8 T-cell ratios and immune senescence in the old elderly population, we investigated whether CMV infection is associated with refractory inversion of CD4/CD8 T-cell ratios and increased phenotypic evidence of immune senescence in HIV infection. An observational cohort study of HIV-infected individuals attending the Newfoundland and Labrador Provincial HIV Clinic in St. John's. CMV infection status was determined by ELISA with infected cell lysate. Expression of CD28 and CD57 on CD8 T cells and cellular immune responses against CMV were measured by flow cytometry. We compared CD4/CD8 T-cell ratios, percentage of CD8 T cells expressing CD28 and percentage of CD8 T cells expressing CD57 between groups of HIV-infected persons discordant for CMV infection. The CMV-seronegative group had significantly higher CD4/CD8 T-cell ratios, more frequent normalization of the ratio to at least 1, and lesser phenotypic evidence of immune senescence. CMV infection is associated with reduced immune reconstitution in HIV infection, even with suppression of HIV replication below detectable levels. This suggests that CMV infection, or some related factor, influences immune resilience in the setting of HIV infection.

Using public T cell responses to predict cytomegalovirus infection status in silico (VIR1P.1004)

Abstract The ability of a host’s adaptive immune system to address an incipient infection relies on the previous existence of T cells which have randomly generated an appropriate antigen-specific T cell receptor (TCR). The nature of V(D)J recombination ensures that despite the enormous space of potential TCRs, there are many TCR specificities that are common in the naïve T cell repertoires across individuals. Hence, many pathogenic antigens are known to induce a “public” T cell response, in which the same functional TCR is found to be immunodominant in multiple individuals. Despite historical limitations on sequencing depth and the limited size of investigational cohorts, previous work on public T cell responses has identified many individual examples of public T cell responses to diseases including CMV, EBV, influenza and others. Using high-throughput TCRβ sequencing, we performed deep characterization of the TCR repertoires of 650 healthy subjects (356 CMV- and 294 CMV+) to enable massively parallel discovery of public T cell responses to CMV. We have identified in one experiment hundreds of CMV-associated public T cell responses. Using cross-validation, we demonstrate that taken collectively public T cell responses to CMV contain enough information to predict CMV status in new subjects using TCR sequencing alone, showing for the first time that assaying the host adaptive immune system could be a valid diagnostic strategy in the context of infectious disease.

Parvovirus B19 (B19) and cytomegalovirus (CMV) infections and anti-erythropoietin (anti-EPO) antibodies in patients on dialysis hyporesponsive to erythropoietin therapy

BackgroundApproximately 10% of patients receiving recombinant human erythropoietin (rHuEPO) do not respond to the treatment. We evaluated parvovirus B19 (B19) and cytomegalovirus (CMV) infections and anti-erythropoietin (anti-EPO) antibodies as potential causes of anemia in dialyzed patients, hyporesponsive to rHuEPO. MethodsData from 120 dialyzed patients, receiving rHuEPO alfa, were collected: demographic characteristics, rHuEPO dose, duration of rHuEPO treatment and time on dialysis, etiology of chronic kidney disease and transfusion history. Serology and PCR were performed to address B19 and CMV infection status. An ELISA was developed to detect anti-EPO antibodies. ResultsrHuEPO resistance correlated with high ferritin levels (p=0.001) and short time on dialysis (p=0.012). B19 DNA was found in 10 (8.3%) dialyzed patients and CMV DNA was detected in 33 (27.5%). There was no significant correlation between B19 infection and anemia, while a tendency of correlation between active CMV infection and hemoglobin levels or hematocrit value (p=0.069 and p=0.070, respectively) has been observed. Anti-EPO antibodies were not detected in any patient. ConclusionsB19 infection is a rare complication in dialyzed patients and should be investigated after exclusion of other common causes, while CMV infection is rather common. The role of CMV infection in the hyporesponsiveness in dialyzed patients should be further evaluated in other studies. Our data suggest that anti-EPO antibodies are not involved in rHuEPO resistance in this population.

Seroprevalence of Cytomegalovirus infection in children aged 0-8 years in Nanjing

Objective To investigate the seroprevalence of Cytomegalovirus (CMV) infection and ages of the children in primary for better understanding the status of CMV infection in China with evidence-based medicine. Methods Total 837 children randomly selected from Nanjing Children's Hospital, from Jun.to Sep.in 2011, including 513 boys and 324 girls, aged from 1 day to 8 years, with mean age of 3.6 years old , were recruited.Serum samples were tested for CMV IgM, CMV IgG, and CMV IgG avidity index using commercial enzyme-linked immunosorbent assay kits. Results Of the total serum samples from 837 children, 690 cases were CMV IgG positive.The overall seroprevalence of CMV IgG was 82.4%, with 83.2% (427/513 cases) and 81.2% (263/324 cases) in boys and girls, respectively.There was no significant difference in the seroprevalence of CMV IgG between boys and girls (χ2=0.584, P=0.445). Of the 92 infants less than 6 months old, 86 cases were CMV IgG positive, and the positive rate was 93.5%.The prevalence gradually declined in infants after 7 months old, fell to the lowest level of 66.7% at age of 9 months, and then constantly maintained around 80.0% from 1 to 8 years old (χ2=15.4, P<0.001). CMV IgM in 352 serum samples were tested, and 23 (6.5%) cases were CMV IgM positive.The positive rate peaked in infants at age of 2-3 months (7/12 cases, 58.3%), then decreased over the age and none of the children older than 6 years were IgM positive (χ2=5.1, P<0.001). Furthermore, the CMV IgG avidity index assay was performed in all 23 cases of IgM positive indivi-duals to estimate the primary CMV infection rate.The results showed low avidity index (<30%) in 13 infants, the primary infection rate was 56.5% (13/23 cases). Most subjects with primary infection (n=7, 53.8%) were younger than 1 year old. Conclusions The current seroprevalence of CMV IgG in children in China was around 80.0%, lower than that in adults, and the primary CMV infection mostly occurred before 3 months of age. Key words: Cytomegalovirus; Seroprevalence; Primary infection; Child

Clinical evaluation of new automated cytomegalovirus IgM and IgG assays for the Elecsys® analyser platform

Cytomegalovirus (CMV) is a leading cause of physical and neurological abnormalities in newborns. Hence, the diagnosis of CMV infection in pregnant women is necessary in order to allow appropriate management of their pregnancy. New assays have been developed for the Roche Elecsys® immunoassay platform that detect CMV-specific immunoglobulin (Ig)M and IgG, with the IgM assay designed to target IgM produced at the start of infection rather than IgM persisting later in infection. This study aimed to evaluate the performance of the new assays compared with other commercial kits widely distributed in laboratories. The performance of the Elecsys and comparator CMV IgM and IgG assays was assessed using 967 preselected patient samples characterised by CMV infection status, as well as being compared using 1,668 unselected clinical samples. The Elecsys CMV IgM and IgG assays performed consistently with comparator assays using the preselected samples. The Elecsys CMV IgM assay showed improved sensitivity compared with the Enzygnost® assay in primary infection (91.2 % vs. 79.4 %) and improved specificity over the Architect® assay in potentially cross-reacting samples (94.1 % vs. 82.4 %). The Elecsys IgM assay reported fewer positive results in the later stages of CMV infection compared with ETI-CYTOK-M ELISA, while the Elecsys IgG assay reported slightly fewer negative results in the early stages of infection compared with ETI-CYTOK-G ELISA. There was good agreement between Elecsys and comparator assays using unselected clinical samples (range 90.4-99.4 %). The Elecsys CMV IgM and IgG assays compare well with routinely used assays and are suitable for clinical use.

An association between cytomegalovirus infection and pre‐eclampsia: a case–control study and data synthesis

Pre-eclampsia shares several similarities with atherosclerotic heart disease. We explored whether, like atherosclerosis, there is a potential link between cytomegalovirus (CMV) infection and pre-eclampsia. CMV IgG, IgM and IgA antibodies were determined by enzyme-linked immunosorbent assays in serums from pre-eclampsia (n = 78), normotensive intrauterine growth restriction (nIUGR) (n = 30) and normal pregnancy controls (n = 109). Data were analyzed by chi-squared, Kruskal-Wallis ANOVA and Mann-Whitney U-tests. Further, we conducted a comprehensive review of published studies on the relation between CMV infection and pre-eclampsia. Risk ratios (RRs) and 95% confidence interval (CI), according to CMV infection status, were calculated using Review Manager. Women with pre-eclampsia had increased CMV IgG seropositivity compared with nIUGR (p < 0.01) and normal pregnancy controls (p < 0.01). In addition, CMV IgG antibody level was higher in pre-eclampsia than normal pregnancy controls (p < 0.001). No difference was observed in CMV IgM or IgA among study groups. Data synthesis revealed that women with CMV infection were at higher risk in the development of pre-eclampsia, compared with women without CMV infection. Combined results for six studies yielded a RR of 1.5 (95% CI 1.2-1.9). CMV infection seems to affect the occurrence of pre-eclampsia. Evaluation of the relation between CMV infection and pre-eclampsia may provide mechanistic insights into pre-eclampsia-related inflammation.

Infection with Cytomegalovirus but not Herpes Simplex Virus induces the accumulation of late differentiated “senescent” T-cells in humans (39.13)

Abstract Infection with the persistent reactivating human cytomegalovirus (CMV) is associated with an age-associated increasing accumulation of late-differentiated CD8+ T-cells even in asymptomatic healthy carriers. It has been postulated that chronic exposure to any repetitively stimulating antigen (”chronic antigenic stress”) will have similar effects. Here, we have analyzed CMV and HSV infection status in the general population. Detailed analysis of T-cell subsets was performed using 10-colour flow cytometry in 100 individuals aged 40-80 yr. T-cells were characterized according to surface expression of CD45RA, CCR7, CD27 and CD28. Our results demonstrate that T-cell subset distribution was similar in CMV-matched, HSV-seropositive and HSV-seronegative individuals, whereas, in line with our and others previous data, individuals harboring CMV had lower frequencies of naïve T-cells (CD45RA+CCR7+CD27+CD28+) ad a reciprocal accumulation of late-differentiated effector memory (CD45RA-CCR7-CD27-CD28-) and TEMRA (CD45RA+CCR7-CD27-CD28-) subsets. These findings emphasize the apparently unique effect of CMV infection on the human immune system, providing evidence that infection with a different persisting herpesvirus does not show any effects similar to the observed large impact of CMV on the proportions of different T-cell subsets. This work was supported by EU 7FP LifeSpan (LSHG-CT-2007-036894), DFG-SFB685-B4 and DFG-PA 361-11/1

Short- and long-term outcomes of using pulmonary allograft donors with low P o2

Background The establishment of lung transplantation as a treatment modality for end-stage lung disease has led to an imbalance in the demand and supply for such a procedure. Increasingly marginal donors are being accepted for transplantation. We assessed the short- and long-term outcomes with the use of lung donors with low P o 2. Methods All heart-lung and double lung transplantations ( n = 362) carried out between 1984 and 2001 were included. Recipients were divided according to the optimized donor P o 2 (on 100% Fi o 2): P o 2 = 30 to 40 kPa = low P o 2 donors ( n = 50) and P o 2 >40 kPa = normal P o 2 donors ( n = 312). There were no differences in the sex distribution, cytomegalovirus infection status, ischemic time, and intubation durations for the recipients and their respective donors between the 2 groups. The low P o 2 donors were older (38 vs 32 years, p = 0.01) and the allografts were transplanted into younger recipients (33 vs 38 years, p = 0.01). Results There was a trend toward an increase in the 30-day mortality between the 2 groups (22% vs 13%, odds ratio 1.92, 95% confidence interval 0.91–4.05 p = 0.08). The 1- and 5-year survival rates (standard error) were 66% (7%) and 52% (7%) for the low P o 2 group and 72% (3%) and 44% (3%) for the normal P o 2 group ( p = 0.97). Similar infection rates were recorded for the groups. Although rejection rates were similar in the first 3 months, there was a lower rate of rejection in the low P o 2 group thereafter, (hazard ratio, 0.52; p = 0.05). Risk of bronchiolitis obliterans syndrome (BOS) onset was marginally increased in the borderline donors (hazard ratio 1.05, 95% confidence interval 0.68–1.62), although this was not statistically significant. Conclusions Donor lung allograft, with optimized P o 2 between 30 and 40 kPa on 100% Fi o 2, used for lung transplantation did compromise 30-day mortality, but the difference in mortality did not extend beyond 30 days in our patient group.

Cytomegalovirus infection status predicts progression of heart-transplant vasculopathy.

Transplant vasculopathy (TVP) is the most common cause of death and retransplantation after heart transplantation. Human cytomegalovirus (HCMV) infection has been linked to atherosclerosis and to the development of TVP. A prospective study evaluating the relation between CMV infection and progression of TVP is lacking thus far. The purpose of the present study was to investigate the influence of CMV infection status on the progression of TVP within 1 year. We enrolled 103 consecutive heart-transplant recipients who underwent routine cardiac catheterization and intracoronary ultrasound examination at study entry and after 1 year. Plaque progression determined by quantitative intracoronary ultrasound was used to define the severity of disease at baseline and at 1-year follow-up. At study entry, HCMV infection status was evaluated by immunological assays and reverse-transcriptase polymerase chain reaction (RT-PCR). HCMV immunoglobulin (Ig)G/IgM seropositivity was found in 34 (33%) of transplant recipients, 11 of whom were HCMV PCR positive. The HCMV-positive group showed more advanced, calcified lesions (64.7% vs. 27.5%, P=0.002), and the maximal plaque thickness was significantly different from the HCMV IgG/IgM-negative group (median [quartile] 1.36 [0.85, 1.88] vs. 1.05 [0.58, 1.34], P=0.02). In a logistic regression model, we demonstrate that HCMV IgG/IgM positivity is a predictor for the progression of TVP independent of cardiovascular risk factors, inflammatory markers, and platelet activation (P=0.038). In addition, HCMV PCR positivity even increases the risk for accelerated TVP (P=0.017) and, consecutively, transplant failure. HCMV infection status in transplant patients detects patients with increased risk for transplant failure caused by TVP.

Usefulness of blood and urine samples collected on filter paper in detecting cytomegalovirus by the polymerase chain reaction technique

A rapid test for the diagnosis of congenital CMV infection is still needed. This study evaluated the usefulness of dried blood and urine samples collected on filter paper for detecting cytomegalovirus (CMV) by the polymerase chain reaction (PCR) assay compared with the use of liquid urine. Samples were obtained from 332 infants aged 1–7 days. Liquid urine samples were collected into bags, cultured in human fibroblasts, and processed using a multiplex PCR technique. Dried urine samples were obtained by placing a piece of filter paper in contact with the infant's genitals. The heels of neonates were punctured and capillary blood was blotted onto filter paper and dried. Dried blood and urine specimens were analyzed by multiplex PCR and nested-PCR assays. A diagnosis of congenital CMV infection was established by isolating the virus, and by detecting viral DNA in the liquid urine. Of the 332 liquid urine samples collected from 332 neonates, seven (2.1%) were positive for CMV and 325 were negative, by both cell culture and PCR assay. In dried samples, CMV DNA was detectable only with a nested PCR assay. Compared with known CMV infection status, 5/7 (71.4%) neonates were positive for congenital CMV infection using dried blood samples. All 325 uninfected neonates were negative. In the dried urine samples, 4/4 CMV-infected infants gave positive tests, and all 262 uninfected infants were negative. Although further improvements in sample collection and/or processing are still needed, PCR testing on dried urine or blood collected on filter paper is a promising approach in the diagnosis of neonatal CMV infection.

Pulmonary diffusion impairment following heart transplantation: a prospective study

The aim of this prospective study was to confirm whether and when a fall in gas transfer occurs following heart transplantation (HT); and to examine the potential relationship between gas transfer and haemodynamic change, immuno-suppression and cytomegalovirus (CMV) infection. The lung physiology of 34 heart transplant recipients (HTR) and 14 control patients undergoing coronary artery bypass grafting (CABG) were studied. The absolute and standardized residual values of forced expiratory volume in one second (FEV1), forced vital capacity (FVC), residual volume (RV), forced residual volume (FRC), total lung capacity (TLC), transfer factor of the lungs for carbon monoxide (TL,CO) and carbon monoxide transfer coefficient (KCO) were measured before and at 30, 60, 90, 120 and 150 days after HT. These data were compared to haemodynamic status, graft rejection, cyclosporin levels and episodes of CMV infection. Lung function was studied in a group of patients before and 4 weeks after CABG. There was a significant fall in mean KCO after HT (pre-HT = 1.29 and post-HT = 1.06 mmol.min-1.kPa.L-1) but not after CABG (pre-CABG = 1.49, post-CABG = 1.5 mmol.min-1.kPa.L-1. No relationship was observed between gas transfer and CMV. At the latest stage following HT (150 days) there was a positive correlation between TL,CO (absolute value and standardized residual) and mean cyclosporin level (r = 0.48 and r = 0.44, respectively) and also between the absolute KCO and actual (r = 0.56) and mean (r = 0.55) cyclosporin levels. Following HT, there is an early fall in gas transfer, which is independent of the effects of surgery and bypass, implicating early immunosuppression (e.g. antithymocyte globulin/cyclosporin).

Cytomegalovirus infection does not increase the risk of vanishing bile duct syndrome after liver transplantation.

Cytomegalovirus (CMV) infection and HLA-DR sharing have been reported to be associated with the development of vanishing bile duct syndrome (VBDS) after liver transplantation. We retrospectively analyzed the importance of these risk factors for VBDS in 126 consecutive recipients of a first transplant. In contrast to previous studies, CMV was monitored strictly using the antigenemia assay, a quantitative marker of the viral load. Patient and graft survival were comparable in patients with and without CMV infection. The incidence of VBDS was low, regardless of the CMV infection status or degree of HLA-DR sharing. Improvements in the early diagnosis and treatment of CMV infection may have eliminated its negative influence on graft survival.