# Tissue Cytomegalovirus DNA Detection by PCR Is Associated with Increased Endoscopic Activity in Ulcerative Colitis: A Retrospective Cohort Study

## TL;DR

This study found that detecting CMV DNA in tissue samples from ulcerative colitis patients is linked to higher disease activity, even without clear signs of infection.

## Contribution

The study shows that tissue CMV DNA detection by PCR is associated with increased endoscopic activity in UC patients, independent of histopathological findings.

## Key findings

- Tissue CMV DNA positivity was found in 37.3% of patients with moderate-to-severe UC.
- Patients with tissue CMV DNA had higher clinical and endoscopic scores compared to those without.
- Serum CMV PCR levels were significantly higher in patients with tissue CMV DNA positivity.

## Abstract

Background: Cytomegalovirus (CMV) reactivation is frequently observed in patients with moderate-to-severe ulcerative colitis (UC), particularly in steroid-refractory cases; however, the clinical significance of tissue CMV DNA detection by polymerase chain reaction (PCR) in the absence of classical histopathological findings remains controversial. Methods: This retrospective cohort study included 110 patients with moderate-to-severe UC who underwent colonoscopy between January 2021 and April 2024 at a tertiary referral center. Tissue and serum samples were analyzed for CMV DNA using PCR. Tissue CMV DNA positivity was defined as ≥250 copies. Endoscopic disease activity was assessed using the Mayo clinical score, Mayo endoscopic score, and the Rachmilewitz Endoscopic Activity Index. Associations between tissue CMV DNA positivity, endoscopic activity scores, inflammatory markers, recent immunosuppressive therapy, and serum CMV PCR results were evaluated. Sensitivity analyses using different tissue CMV DNA thresholds and receiver operating characteristic (ROC) curve analysis for serum CMV PCR were also performed. Results: Tissue CMV DNA positivity was detected in 37.3% of patients. Patients with tissue CMV DNA positivity had significantly higher Mayo clinical scores and Rachmilewitz Endoscopic Activity Index scores compared with CMV-negative patients, whereas Mayo endoscopic scores did not differ significantly between groups. Serum CMV PCR levels were markedly higher in patients with tissue CMV DNA positivity (p < 0.001). Tissue CMV DNA copy number showed a strong correlation with serum CMV PCR levels but did not demonstrate a consistent linear association with endoscopic activity scores. In multivariable logistic regression analysis, recent corticosteroid use was independently associated with tissue CMV DNA positivity, while anti-TNF therapy and endoscopic activity indices were not independent predictors. ROC analysis demonstrated good diagnostic performance of serum CMV PCR for predicting tissue CMV DNA positivity (AUC = 0.82). Conclusions: In patients with moderate-to-severe UC, tissue CMV DNA positivity (≥250 copies) is associated with increased clinical and endoscopic disease activity, even in the absence of classical histopathological evidence of CMV infection. These findings suggest that molecular detection of CMV in colonic tissue may provide clinically relevant information in selected patient populations, particularly those with recent corticosteroid exposure. However, tissue CMV DNA positivity should be interpreted as a molecular association rather than definitive evidence of causality or an indication for antiviral therapy. Prospective multicenter studies are warranted to further clarify the clinical implications of tissue CMV DNA detection in UC.