# Genetic proof of herpesviruses CMV, EBV and HHV-6 in intestinal biopsies from patients with inflammatory bowel diseases: prevalence and disease characteristics

## TL;DR

This study finds that EBV is common in IBD patients and linked to more severe disease, while HHV-6 is associated with certain treatments.

## Contribution

The study is the first to report the prevalence of EBV and HHV-6 in IBD patients and their associations with disease severity and treatment.

## Key findings

- EBV was detected in 25.7% of IBD patients and linked to higher disease activity and longer hospitalization.
- HHV-6 was found in 8.7% of patients and associated with specific immunosuppressive therapies.
- CMV was detected in 6.1% of patients but showed fewer associations with disease characteristics.

## Abstract

While the clinical relevance of cytomegalovirus (CMV) for inflammatory bowel disease (IBD) patients remains controversial, the role of related Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV-6) is unknown. The aim of this retrospective study was to determine the prevalence of CMV, EBV, and HHV-6 DNA in the intestinal mucosa of IBD patients, and to identify potential risk factors and associations with disease characteristics.

Any IBD patient who underwent endoscopy with mucosal biopsy for virologic assessment at Heidelberg University Hospital from December 2018 to September 2020 was eligible. DNA of CMV, EBV, and HHV-6 was determined by polymerase chain reaction.

A total of 230 patients were included (123 male, median age 37 years). Ulcerative colitis was diagnosed in 146 patients (63.5%), Crohn’s disease in 78 patients (33.9%), and unclassified IBD in 6 patients (2.6%). The prevalence of CMV was 6.1% (n = 14/230), 25.7% for EBV (n = 59/230), and 8.7% for HHV-6 (n = 20/230). Detection of EBV DNA was associated with longer hospitalization (P = 0.001), steroid treatment (P = 0.004), higher CRP levels (P = 0.04), and higher disease activity (P = 0.02). Histological evidence of inflammation (P = 0.03) and ulcers were also detected significantly more often in EBV-positive patients (P = 0.001). JAK-inhibitor treatment was associated with CMV infection, while HHV-6-positive patients were treated more frequently with azathioprine/6-mercapotopurine or steroids.

The study reveals that the prevalence of EBV in the intestinal mucosa is high in patients with IBD and correlates with disease activity and severity, while HHV-6 is associated with specific immunosuppressive therapy.