Brief Article
Copyright ©2011 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Mar 7, 2011; 17(9): 1185-1191
Published online Mar 7, 2011. doi: 10.3748/wjg.v17.i9.1185
Diagnostic value of antigenemia assay for cytomegalovirus gastrointestinal disease in immunocompromised patients
Naoyoshi Nagata, Masao Kobayakawa, Takuro Shimbo, Kazufusa Hoshimoto, Tomoyuki Yada, Takuji Gotoda, Junichi Akiyama, Shinichi Oka, Naomi Uemura
Naoyoshi Nagata, Masao Kobayakawa, Takuji Gotoda, Junichi Akiyama, Department of Gastroenterology and Hepatology, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjyuku-ku, Tokyo, 162-8655, Japan
Takuro Shimbo, Department of Clinical Research and Informatics International Clinical Research Center Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjyuku-ku, Tokyo, 162-8655, Japan
Kazufusa Hoshimoto, Department of Clinical Laboratory Pathological Division, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjyuku-ku, Tokyo, 162-8655, Japan
Tomoyuki Yada, Naomi Uemura, Department of Gastroenterology and Hepatology, National Center for Global Health and Medicine, Kohnodai Hospital, 1-7-1 Kohnodai, Ichikawa city, Chiba, 272-8516, Japan
Shinichi Oka, Division of Aids Clinical Center, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjyuku-ku, Tokyo, 162-8655, Japan
Author contributions: Nagata N participated in the design of the study, data acquisition and interpretation, performed endoscopy, and wrote the manuscript; Kobayakawa M participated in the design of the study and performed endoscopy; Shimbo T participated in the design of the study and contributed to evaluation for statistical analysis; Hoshimoto K made the pathological diagnosis and contributed to the writing of the manuscript; Yada T and Akiyama J performed endoscopy and contributed to the writing of the manuscript; Gotoda T, Oka S and Uemura N contributed to the writing of the manuscript; all authors read and approved the submitted version of the manuscript.
Correspondence to: Naoyoshi Nagata, MD, Department of Gastroenterology and Hepatology, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan. nnagata_ncgm@yahoo.co.jp
Telephone: +81-3-32027181 Fax: +81-3-32071038
Received: October 13, 2010
Revised: January 5, 2011
Accepted: January 12, 2011
Published online: March 7, 2011
Abstract

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/mm3. 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.

Keywords: Cytomegalovirus; Gastrointestinal disease; Antigenemia assay; Real-time polymerase chain reaction; Human immunodeficiency virus infection