Comparison Diagnostic Tests for the Diagnosis of CYTOmegalovirus Organ Disease in Patients With intestinalBOweL Diseases

Patients with chronic inflammatory bowel disease (IBD) are subject to an increased risk of infectious events. This is secondary in part to an intrinsic dysregulation of the immune system, in part to the increasingly frequent need to subject the patient to immunomodulatory therapies for the management of the underlying disease. In this context, it is very difficult from a clinical point of view to be able to demonstrate a concomitant intestinal cytomegalovirus (CMV) organ disease, since the symptoms are often nonspecific or overlapping. Following the guidelines, since there is no well-defined cut-off for viral replication in blood, the gold standard for the diagnosis of intestinal CMV disease remains organ-specific biopsy with immunohistochemical research of the included nuclei. However, at the moment there are no reliable findings for this method that can distinguish a clinically insignificant reactivation from a true organ disease. However, plasma CMV viremia measurement is generally recommended in this setting since active replication in blood could be an epiphenomenon of organ disease. Similarly, some studies have shown a correlation between CMV gastroenteritis and detection of CMV-DNA in fecal samples. Furthermore, several methods have been developed in recent years, and their diagnostic yield has not yet been fully defined. The evaluation of viral load on tissue biopsy by PCR is a method that is gaining ground, and currently the guidelines suggest it in association with immunohistochemistry itself. Some authors suggest a cut-off of 250 cp/mg of tissue to define organ disease. In this setting, the initiation of a specific antiviral treatment remains non-standardized, and it presents expected side effects, primarily bone marrow suppression. However, in several studies, an increased need for surgery for uncontrolled underlying disease has been found in patients with CMV organ disease who are not treated promptly.

From a clinical point of view, in patients who have worsening symptoms related to IBD, being able to identify early markers able to predict CMV colonic organ disease is of crucial importance, since early specific treatment could increase the chances of a favorable outcome, sparing the patient the need for abdominal surgery. In this context, plasma and fecal CMV-DNA dosage represents a rapid diagnostic method, with a turn-over of about 24 hours, which could be an epiphenomenon of the colonic disease itself.

The primary objective of the study is to evaluate the diagnostic performance of different methods used for the diagnosis of CMV infection, namely CMV-DNA on blood and CMV-DNA on fecal samples - comparing them with the gold standard, namely immunohistochemical investigation on biopsy sample in patients affected by IBD with clinical worsening requiring hospitalization.

• Concordance Between Positive/Borderline Immunohistochemistry and PCR for CMV on Biopsy Samples [Time frame: Each samples taken from the patients will be tested through study completion (average of 2 year)]
• Severity of Immunohistochemical Pattern and Its Relationship with Clinical Evolution [Time frame: Each samples taken from the patients will be tested through study completion (average of 2 year)]
• Viral Load in Biopsy Samples and Its Correlation with Clinical Outcomes [Time frame: Each samples taken from the patients will be tested through study completion (average of 2 year)]
• Impact of Antiviral Treatment on Clinical Evolution [Time frame: Each samples taken from the patients will be tested through study completion (average of 2 year)]
• Clinical Evolution at 30 Days in Patients With and Without CMV Organ Disease [Time frame: At the follow-up at 30 days (through study completion, an average of 2 year)]