Cytomegalovirus Detection by PCR on Fresh and Formalin-Fixed Colon Tissue Biopsies of Children with Colitis: A Prospective Cohort Study.

Abstract

Background: Diagnosis of cytomegalovirus (CMV) in biopsies relies on detecting classic viral cytopathic effects (CPE) in tissue. These effects are not always apparent, and confirmatory tests are necessary. This study aimed to compare the results of the different diagnostic tests for CMV detection in colitis, including PCR on fresh and formalin-fixed paraffin-embedded (FFPE) tissue, immunohistochemistry (IHC), histology, and plasma PCR, in association with the clinical course.

Methods: In this prospective study, CMV-PCR was performed on fresh tissue (FT) and FFPE tissue, and IHC was conducted on colon biopsies from 153 children with colitis referred to Children Medical Center Hospital (Tehran, Iran) from 2015 to 2019. The results of different diagnostic methods were evaluated in association with the clinical and histopathological findings.

Results: Fifty out of 153 (32%) cases had positive FT-CMV PCR. Forty of these fifty positive samples and 21 of 103 negative ones had concomitant FFPE biopsy tissue. FFPE-PCR and IHC were positive in 17 (42.5 %) and 2 (5%) out of 40 FT-PCR-positive cases, respectively. The two IHC-positive cases had positive FFPE-PCR and high CMV-DNA plasma levels and showed histologically active colitis and CPE. Remarkably, 14 (35%) cases were identified with positive FT-PCR without any evidence of colitis in histopathology. During follow-up, FT-PCR-positive inflammatory bowel disease (IBD) cases treated with antiviral drugs showed a poorer outcome than the non-treated cases (P=0.03).

Conclusion: A high positive rate was observed for both FT- and FFPE-CMV PCR, with a poor association with histology. IHC positivity was associated with high plasma CMV DNA levels and the presence of CPE. The efficacy of anti-CMV treatment in colitis cases should be verified through randomized controlled clinical trials. A preprint version of this article is available online at doi: 10.22541/au.168052684.43457923/v1.