P0207A combination of cytomegalovirus immunohistochemistry and quantitative tissue PCR improves biochemical outcomes in IBD patients

Background Cytomegalovirus (CMV) colitis may complicate inflammatory bowel disease (IBD).1 While immunohistochemistry (IHC) and quantitative tissue PCR (qPCR) are recognised as essential diagnostic tests, their routine combined use has not yet been established as standard practice.1-3 Evidence also remains limited regarding thresholds distinguishing latent from active CMV infection; Roblin et al suggested a viral load cut-off of > 250 viral copies/mg tissue.1-3 This study aimed to evaluate the diagnostic value of combining IHC and tissue qPCR to guide treatment decisions. Methods We retrospectively analysed 110 diagnostic colonoscopies performed at our IBD centre between 2020 and 2024, with combined CMV-IHC and tissue qPCR testing. Biopsies were obtained from the most inflamed regions based on clinical suspicion of CMV infection. IHC and qPCR were carried out at affiliated pathology and virology departments. Concordance between IHC and qPCR was assessed using Cohen’s kappa. qPCR viral loads (CMV-DNA copies/ml = co/ml) were summarised as median (range). CMV-positive patients received antiviral therapy with ganciclovir and/or valganciclovir at the physician’s discretion. Faecal calprotectin (CPT) and C-reactive protein (CRP) were summarised as median (range) and compared between pre-treatment and a median of one week post-treatment using the Wilcoxon matched-pairs signed-rank test or paired t-test. Results Of 110 cases, 6 (5.5%) were IHC positive/qPCR positive (group 1), 10 (9.1%) IHC negative/qPCR positive (group 2), 2 (1.8%) IHC positive/qPCR negative (group 3), and 92 (83.6%) IHC negative/qPCR negative (group 4). Overall concordance between IHC and qPCR was 89% (moderate agreement, κ = 0.448, p = 0.003). Median viral load was 11600 co/ml [IQR 533–25000] in group 1 and 3050 co/ml [IQR 530–5000] in group 2, indicating higher viral loads in IHC-positive samples. Overall viral load in group 2 was ≥ 450 co/ml. 17 of 18 CMV-positive patients received antiviral treatment; 5 receiving concomitant corticosteroids or topical 5-ASA were excluded, 3 datasets were missing. In the remaining cohort, CPT decreased from 2371 µg/g to 438 µg/g and CRP from 1.46 mg/dl to 0.43 mg/dl. In group 2, CPT decreased from 1719 µg/g to 265 µg/g, and CRP from 1.05 mg/dl to 0.28 mg/dl. A data overview is provided in table 1. Conclusion Combined CMV-IHC and tissue qPCR testing detects clinically meaningful infection missed by IHC alone. Antiviral treatment of qPCR-positive patients with > 450 co/ml viral load (even when IHC-negative) significantly reduces inflammatory markers, supporting routine dual testing and viral load guided therapy in IBD. References: 1. Soni K, Puing A. Cytomegalovirus Colitis in Adult Patients with Inflammatory Bowel Disease. Viruses. 2025; 17(6): 752. https://doi.org/10.3390/v17060752 2. Kucharzik T, Ellul P, Greuter T, et al. ECCO Guidelines on the Prevention, Diagnosis, and Management of Infections in Inflammatory Bowel Disease. J Crohns Colitis. 2021; 15(6): 879-913. doi: 10.1093/ecco-jcc/jjab052 3. Wang G, Zhao J, Jiang J, Huang A, Ye L, Jiang Z. The Positive Immunohistochemical Staining of Cytomegalovirus in Colon Biopsy Samples Suggests That the Viral DNA Load in qPCR Is High. Int J Surg Pathol. 2025; 33(8): 1752-58. doi: 10.1177/10668969251339808 Conflict of interest: Dr. Strasser, Florian: Travel support and speaker honoraria from Abbvie. Travel support from Johnson & Johnson. No other conflicts of interest are declared. Müller, Antonia: Travel support and speaker honoraria from Abbvie. Travel support from Johnson & Johnson. No other conflicts of interest are declared. Steidl, Karin: Travel support and speaker honoraria from Abbvie, Takeda, Falk Johnson & Johnson Astropharma Afasigma MSD Boston Scientific No other conflicts of interest are declared Gröchenig, Hans Peter: Travel support and speaker honoraria from Abbvie, Takeda, Lilly and Johnson & Johnson