title: Cytomegalovirus load in inflamed intestinal tissue is predictive of resistance to immunosuppressive therapy in ulcerative colitis.
abstract: OBJECTIVE
  Previous studies have suggested an association between cytomegalovirus (CMV) infection and steroid-refractory inflammatory bowel disease. In this study, the use of CMV DNA load during acute flare-ups of ulcerative colitis (UC) to predict resistance to immunosuppressive therapy was evaluated in intestinal tissue.
  
  
  METHODS
  Forty-two consecutive patients (sex ratio M/F: 0.9, mean age: 43.6 years) hospitalized for moderate to severe UC and treated with IV steroids were included prospectively. A colonoscopy was performed for each patient at inclusion; colonic biopsy samples of the pathological tissue, and if possible, of the healthy mucosa, were tested for histological analysis and determination of CMV DNA load by real-time polymerase chain reaction assay. Patients were treated as recommended by the current guidelines.
  
  
  RESULTS
  Sixteen patients were found positive for CMV DNA in inflamed intestinal tissue but negative in endoscopically healthy tissue; all of these patients were positive for anti-CMV IgG, three exhibited CMV DNA in blood, and none was positive for intestinal CMV antigen by immunohistochemistry detection. In the 26 remaining patients, no stigmata of recent CMV infection were recorded by any technique. By multivariate analysis, the only factor associated with CMV DNA in inflammatory tissue was the resistance to steroids or to three lines of treatment (risk ratio: 4.7; 95% confidence interval: 1.2-22.5). A CMV DNA load above 250 copies/mg in tissue was predictive of resistance to three successive regimens (likelihood ratio+=4.33; area under the receiver-operating characteristic curve=0.85). Eight UC patients with CMV DNA in inflamed tissue and therapeutic failure received ganciclovir; a clinical remission was observed in seven cases, with a sustained response in five of them.
  
  
  CONCLUSIONS
  The CMV DNA load determined in inflamed intestinal tissue predicts resistance to steroid treatment and to three drug regimens in UC. Initiation of an early antiviral treatment in these patients might delay the occurrence of resistance to current treatments.
authors.affiliation: University of Lyon, Saint-Etienne, France. xavier.roblin@chu-st-etienne.fr
authors.forename: Xavier
authors.initials: X
authors.lastname: Roblin
authors.forename: Sylvie
authors.initials: S
authors.lastname: Pillet
authors.forename: Abderrahim
authors.initials: A
authors.lastname: Oussalah
authors.forename: Philippe
authors.initials: P
authors.lastname: Berthelot
authors.forename: Emilie
authors.initials: E
authors.lastname: Del Tedesco
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Phelip
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Chambonnière
authors.forename: Olivier
authors.initials: O
authors.lastname: Garraud
authors.forename: Laurent
authors.initials: L
authors.lastname: Peyrin-Biroulet
authors.forename: Bruno
authors.initials: B
authors.lastname: Pozzetto
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D003587:Cytomegalovirus / Q000276:immunology / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000150:complications* / Q000188:drug therapy / Q000276:immunology / Q000821:virology*; D004279:DNA, Viral / Q000032:analysis / Q000097:blood; D004351:Drug Resistance; D005260:Female; D015774:Ganciclovir / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007413:Intestinal Mucosa / Q000821:virology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D019562:Viral Load
chemical_list: D000305:Adrenal Cortex Hormones; D000914:Antibodies, Viral; D000998:Antiviral Agents; D004279:DNA, Viral; D007166:Immunosuppressive Agents; D015774:Ganciclovir