Impact of the Presence of Epstein-Barr Virus in Intestinal Mucosa of Inflammatory Bowel Disease Patients

Background To evaluate the importance of positive Epstein–Barr virus (EBV) status in intestinal biopsy in patients with inflammatory bowel disease (IBD), its association with active disease and immunosuppressive (IM) therapy and its influence on the clinical evolution of IBD. Methods We retrospectively analysed patients with IBD who were tested for EBV in intestinal mucosa between November 2009 and June 2017. Pathologists decided EBV testing based on the presence of severe histologic activity with/without prominent lymphoplasmacytic infiltrate or refractory disease to various treatments. We analysed phenotypic characteristics, previous treatments, active therapies at the time of EBV testing, EBV status by immunohistochemistry, presence of lymphoma, treatment decision making after EBV testing and subsequent clinical evolution based on hospital admissions and treatment escalation requirement. Results We included 56 patients, 28 with Crohn’s disease (CD) and 28 with ulcerative colitis (UC). The predominant phenotype of patients with CD was A2L3C1. Regarding patients with UC, 14 patient had left-sided and 14 extensive colitis. EBV was positive (EBV+) in 26 cases (46%), one of them associated with a lymphoproliferative disorder. EBV+ status was associated with clinically active disease (53.3% vs. 25%, p = 0.08); severe endoscopic (54.5% vs. 37.5%, p = 0.02) and severe histological activity (72.2% vs. 33.3%, p = 0.007) and the presence of a prominent lymphoplasmacytic infiltrate (68.8% vs. 16.7%, p < 0.0005). In addition, active steroid treatment, but not IM and/or biological therapy, at the time of EBV testing was associated with EBV+ status (61.5% vs. 33.3%, p = 0.03). Only the presence of a prominent lymphoplasmacytic infiltrate showed significant association with EBV+ in the multivariate analysis (p = 0001). IM therapy was de-escalated in 6/26 EBV-positive patients. In EBV- patients, IM treatment was escalated in 10/30. After a mean follow-up of 53.3 months, 17 patients required hospital admission and 26 escalation of therapy. Both risk of admissions and escalation of treatment during follow-up were higher in EBV+ patients (38.5% vs. 23.3%, p = 0.2; and 65.4% vs. 30%, p = 0.008, respectively). Only female sex was associated with a greater possibility of hospital admission and EBV+ with the need for treatment escalation (p = 0.03) in the multivariate analysis. None of the patients developed lymphoma during follow-up. Conclusion EBV+ status in intestinal mucosa is associated with histological activity. Prominent lymphoplasmacytic infiltrate is the only factor associated with EBV+ status independently of immunosuppression status. EBV+ is associated with subsequent poor clinical evolution and a greater need for escalation of IM therapy.