Alimentary TractPrevalence, detection rate and outcome of cytomegalovirus infection in ulcerative colitis patients requiring colonic resection
Introduction
Active ulcerative colitis (UC) and steroid-refractory UC are a challenge for gastroenterologists. Treatment options, represented by immunomodulator therapies, although characterised by slow therapeutic effect and significant side effects, are usually effective. However, a significant proportion of patients with steroid-refractory UC require proctocolectomy.
Causes of the resistance are still not well defined, but several reports in recent years have sought to identify the role of superimposed infections.
In particular, cytomegalovirus (CMV) infection has frequently been found with variable prevalence in UC patients and has been proposed as a pathogen contributing to flares of steroid-resistant colitis. However, its exact pathogenic role in UC remains unclear. Since CMV is a common infection, occurring in 40–100% of the general population [1], and persisting indefinitely within the host, it is unclear whether CMV is a bystander or has a primary role in the reactivation of colitis or in corticosteroid-resistant colitis [2].
It has been shown that rectal detection and antiviral treatment of CMV in a steroid-refractory UC candidate to proctocolectomy can avoid the need for surgery [3], [4]. However, it is not clear whether CMV infection can be accurately detected in rectal or colic biopsies prior to surgery, and whether it has a role in the steroid-resistant process leading to surgery.
The objectives of our study were to determine the prevalence of CMV infection in surgical specimens and in pre-operative endoscopic biopsy specimens of UC patients who required surgery, and to assess the role of concomitant and past use of steroids or immunosuppressive treatments in the presence of CMV.
We also evaluated UC patients with unrecognised and untreated CMV infection, in terms of clinical outcome and CMV reactivation following colectomy.
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Patients and methods
Seventy-seven consecutive UC patients (43 males and 34 females) regularly followed at the Department of Gastroenterology of L. Sacco University Hospital, underwent proctocolectomy between September 1997 and March 2003 at the Department of Surgery of the same hospital. Reasons for surgery were (a) intractable steroid-refractory UC in 55 patients, (b) loss of function of the colon or inability to control symptoms despite quiescent disease in 9 patients, (c) toxic megacolon in 6 patients and (d)
Prevalence of CMV in refractory and non-refractory UC
Fifteen of 55 patients with steroid-refractory UC (27.3%) and 2 of 22 non-refractory patients (9.1%) were positive for CMV by immunohistochemistry (p = 0.123).
Typical CMV inclusions were found in 16 surgical specimens and in 6 of 74 pre-operative biopsy specimens (54 from steroid-refractory and 20 from non-refractory UC patients).
Detection of CMV inclusions in biopsy specimens was not related to the number of biopsies or to the time elapsed since colonoscopy and index surgery (Table 2).
Of six
Discussion
The clinical significance of CMV infection in patients with inflammatory bowel diseases is still uncertain. In particular, whether CMV behaves as a non-pathogenetic bystander in the intestine or has a crucial role in triggering the onset of or maintaining inflammation is a matter of debate. A body of literature has shown that CMV infection is specifically associated with and thought to be a cause of steroid-refractory UC, but the strength and nature of this association are controversial.
Our
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