Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 14, 2016; 22(6): 2030-2045
Published online Feb 14, 2016. doi: 10.3748/wjg.v22.i6.2030
Cytomegalovirus and ulcerative colitis: Place of antiviral therapy
Sylvie Pillet, Bruno Pozzetto, Xavier Roblin
Sylvie Pillet, Bruno Pozzetto, Xavier Roblin, Groupe Immunité des Muqueuses et Agents Pathogènes (GIMAP)-EA3064, Faculty of Medicine of Saint-Etienne, University of Lyon, 69365 Lyon Cedex 7, France
Sylvie Pillet, Bruno Pozzetto, Laboratory of Infectious Agents and Hygiene, University Hospital of Saint-Etienne, 42025 Saint-Etienne Cedex 2, France
Xavier Roblin, Department of Gastroenterology, University Hospital of Saint-Etienne, 42025 Saint-Etienne Cedex 2, France
Author contributions: Pillet S, Pozzetto B and Roblin X contributed to perform the previous studies related to this review, to review in-depth the available literature, to write the manuscript and to approve all the successive versions, including the last one.
Conflict-of-interest statement: The authors have no conflict of interest to declare.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Xavier Roblin, MD, PhD, Professor, Department of Gastroenterology, University Hospital of Saint-Etienne, 42055 Saint-Etienne Cedex 2, France.
Telephone: +33-4-77828985 Fax: +33-4-77828452
Received: September 9, 2015
Peer-review started: September 10, 2015
First decision: October 14, 2015
Revised: November 19, 2015
Accepted: December 19, 2015
Article in press: December 19, 2015
Published online: February 14, 2016

The link between cytomegalovirus (CMV) infection and inflammatory bowel diseases remains an important subject of debate. CMV infection is frequent in ulcerative colitis (UC) and has been shown to be potentially harmful. CMV reactivation needs to be diagnosed using methods that include in situ detection of viral markers by immunohistochemistry or by nucleic acid amplification techniques. Determination of the density of infection using quantitative tools (numbers of infected cells or copies of the genome) is particularly important. Although CMV reactivation can be considered as an innocent bystander in active flare-ups of refractory UC, an increasing number of studies suggest a deleterious role of CMV in this situation. The presence of colonic CMV infection is possibly linked to a decreased response to steroids and other immunosuppressive agents. Some treatments, notably steroids and cyclosporine A, have been shown to favor CMV reactivation, which seems not to be the case for therapies using anti-tumor necrosis factor drugs. According to these findings, in flare-ups of refractory UC, it is now recommended to look for the presence of CMV reactivation by using quantitative tools in colonic biopsies and to treat them with ganciclovir in cases of high viral load or severe disease.

Keywords: Human cytomegalovirus, Ulcerative colitis, Inflammatory bowel disease, Ganciclovir, Viral load, Flare-up, Inflammation, Intestinal mucosa, Quantitative polymerase chain reaction

Core tip: There is increasing evidence for the deleterious effect of in situ cytomegalovirus (CMV) reactivation in flare-ups of refractory ulcerative colitis. In patients aged > 30 years with a high density of infection in the colonic tissue, or with stigmata of severe disease associated with colonic markers of CMV reactivation (whatever the density of infection), treatment with ganciclovir is highly recommended, together with anti-tumor necrosis factor monoclonal antibody therapy in the absence of any contraindication to these drugs. For validating the present strategy based on our experience and the in-depth analysis of the available literature presented in this review, prospective randomized controlled studies are urgently needed.