Abstract/Text: AIM: To investigate the utility of the cytomegalovirus (CMV) antigenemia assay for the diagnosis of CMV gastrointestinal disease (GID).
METHODS: One hundred and thirty immunocompromised patients were enrolled in this study. Patients with a history of anti-CMV treatment and who had not undergone examination using the antigenemia assay were excluded. CMV-GID was defined as the detection of large cells with intranuclear inclusions alone or associated with granular cytoplasmic inclusions by biopsy. Biopsy sections were stained with hematoxylin and eosin and immunohistochemically stained with anti-CMV. We evaluated the association between CMV-GID and patient characteristics (symptoms, underlying disease, medication, leukocyte counts, and antigenemia assay). All patients were checked with an human immunodeficiency virus (HIV) antibody test before endoscopic examination. White blood cell (WBC) counts were obtained from medical records within 1 wk of endoscopy. Leukopenia was defined as a total WBC count < 5000 cells/mm(3). For HIV patients, we also checked CD4+ counts from medical records.
RESULTS: A total of 99 patients were retrospectively selected for analysis. Of the immunocompromised patients, 19 had malignant disease, 18 had autoimmune disease, 19 had disorders of biochemical homeostasis, three had undergone transplantation, and 45 had HIV infection. A total of 50 patients had received immunosuppressive therapy. No patients had inflammatory bowel disease. Fifty-five patients were diagnosed as having CMV-GID. Univariate analysis indicated an association between HIV infection, leukopenia, and positive antigenemia and CMV-GID (P < 0.05). Multivariate analysis using logistic regression revealed that HIV infection and positive antigenemia were the only independent factors related to CMV-GID (P < 0.01). The sensitivity, specificity, positive predictive value, and negative predictive value of antigenemia for CMV-GID were 65.4%, 93.6%, 91.9%, and 71.0%, respectively. In a subgroup analysis, patients with leukopenia displayed low sensitivity and high specificity. Minimal differences in accuracy were seen among patients with or without leukopenia. HIV-infected patients displayed low sensitivity and high specificity. Accuracy barely differed between HIV-positive and -negative patients. In HIV-infected patients, CD4 count < 50 cells/μL resulted in low sensitivity and high specificity. Differences in accuracy among patients were minor, regardless of CD4 count. In patients who had undergone both quantitative real-time polymerase chain reaction (PCR) and antigenemia assay, real-time PCR was slightly more accurate in terms of sensitivity than the antigenemia assay; however, this difference was not statistically significant (P = 0.312).
CONCLUSION: If the antigenemia test is positive, endoscopic lesions are acceptable for the diagnosis of CMV-GID without biopsy. The accuracy is not affected by HIV infection and leukopenia. Either PCR or the antigenemia assay are valid.

Abstract/Text: Of 149 patients with suspected cytomegalovirus (CMV) gastrointestinal disease, 51 (36%) confirmed cases, 6 (4%) probable cases, and 64 (45%) instances of non-CMV gastrointestinal disease were analyzed using the CMV antigenemia assay; 22 patients (5%) with indeterminate gastrointestinal disease were excluded. The sensitivity and specificity of the CMV antigenemia assay (defined as detection of > or =1 positive cells per 200,000 leukocytes) for diagnosis of CMV gastrointestinal disease were 54% (95% confidence interval, 41%-68%) and 88% (95% confidence interval, 77%-94%), respectively.

Abstract/Text: We prospectively evaluated a risk-adapted pre-emptive treatment with ganciclovir for CMV diseases in patients undergoing allogeneic bone marrow transplantation (BMT). High-level CMV antigenemia (10 or more positive cells on two slides) or CMV antigenemia at any level in patients with grade II-IV acute graft-versus-host disease (aGVHD) were chosen as risk factors. We also retrospectively evaluated virus reactivation in plasma using quantitative real-time polymerase chain reaction (PCR). Fifty patients were evaluable. None of the 27 patients with or without grade I aGVHD developed high-level CMV antigenemia or CMV disease. Among the 23 patients with grade II-IV aGVHD, 12 patients (52%) developed CMV antigenemia and were treated pre-emptively, of whom two developed CMV gastroenteritis or retinitis in spite of therapy. Six of the remaining 11 patients developed CMV gastroenteritis before CMV antigenemia was detectable. All of the eight patients with CMV diseases were successfully treated with ganciclovir and no deaths directly related to CMV disease occurred. In four of the seven evaluable patients with CMV gastroenteritis, real-time PCR was able to detect virus reactivation earlier than CMV antigenemia. Although our risk-adapted pre-emptive therapy effectively reduced CMV-related mortality, further refinements of this approach, particularly in the prevention of CMV gastroenteritis, may be achieved by incorporating real-time PCR.

Abstract/Text: We studied the main clinical features, outcome, and laboratory parameters in a group of solid organ transplant (SOT) patients with immunohistochemically proven cytomegalovirus (CMV) disease. Confirmed CMV cases were obtained through databases. Demographics, clinical data, transplantation type, immunosuppressive regimens, donor and recipient CMV serostatus, therapy, outcome and laboratory results, pp65 antigenemia, and qualitative polymerase chain reaction (PCR) for CMV were analyzed. From 1995 to 2004, 31 cases with complete medical records were identified. Disease appeared between 24 and 2538 days after transplantation but most cases presented in the first 100 days. Gastrointestinal CMV disease was the most frequent form (71%), while thrombocytopenia was present in 50% of cases, and leukopenia was less common (35.5%). CMV pp65 antigenemia was positive in 58% of patients, but its sensitivity increased to 71% if performed during the first 6 months. A qualitative CMV PCR technique gave similar results during this period (71.4%). Most patients were treated with intravenous ganciclovir (n=25; 80.6%). In 4 cases (19.4%), use of foscarnet alone or a sequential regimen with ganciclovir-foscarnet was deemed necessary. Surgical procedures were necessary in 5 patients (16%). The death rate reached 13%. CMV end-organ disease can be a life-threatening infection in SOT patients. Gastrointestinal disease was the most frequent end-organ disease. CMV antigen detection is best suited for the early period after transplantation.