title: Human cytomegalovirus and Epstein-Barr virus infection in inflammatory bowel disease: need for mucosal viral load measurement.
abstract: OBJECTIVE
  To evaluate the best diagnostic technique and risk factors of the human Cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) infection in inflammatory bowel disease (IBD).
  
  
  METHODS
  A cohort of 40 IBD patients (17 refractory) and 40 controls underwent peripheral blood and endoscopic colonic mucosal sample harvest. Viral infection was assessed by quantitative real-time polymerase chain reaction and immunohistochemistry, and correlations with clinical and endoscopic indexes of activity, and risk factors were investigated.
  
  
  RESULTS
  All refractory patients carried detectable levels of HCMV and/or EBV mucosal load as compared to 13/23 (56.5%) non-refractory and 13/40 (32.5%) controls. The median DNA value was significantly higher in refractory (HCMV 286 and EBV 5.440 copies/10(5) cells) than in non-refractory (HCMV 0 and EBV 6 copies/10(5) cells; P < 0.05 and < 0.001) IBD patients and controls (HCMV and EBV 0 copies/10(5) cells; P < 0.001 for both). Refractory patients showed DNA peak values ≥ 10(3) copies/10(5) cells in diseased mucosa in comparison to non-diseased mucosa (P < 0.0121 for HCMV and < 0.0004 for EBV), while non-refractory patients and controls invariably displayed levels below this threshold, thus allowing us to differentiate viral colitis from mucosal infection. Moreover, the mucosal load positively correlated with the values found in the peripheral blood, whilst no correlation with the number of positive cells at immunohistochemistry was found. Steroid use was identified as a significant risk factor for both HCMV (P = 0.018) and EBV (P = 0.002) colitis. Finally, a course of specific antiviral therapy with ganciclovir was successful in all refractory patients with HCMV colitis, whilst refractory patients with EBV colitis did not show any improvement despite steroid tapering and discontinuation of the other medications.
  
  
  CONCLUSIONS
  Viral colitis appeared to contribute to mucosal lesions in refractory IBD, and its correct diagnosis and management require quantitative real-time polymerase chain reaction assay of mucosal specimens.
authors: Rachele Ciccocioppo, Francesca Racca, Elena Betti, Gino Roberto Corazza, Centre for the Study and Cure of Inflammatory Bowel Disease, Clinica Medica I, IRCCS San Matteo Hospital Foundation, University of Pavia, 27100 Pavia, Italy.
authors: Rachele
authors: R
authors: Ciccocioppo
authors: Rachele Ciccocioppo, Francesca Racca, Elena Betti, Gino Roberto Corazza, Centre for the Study and Cure of Inflammatory Bowel Disease, Clinica Medica I, IRCCS San Matteo Hospital Foundation, University of Pavia, 27100 Pavia, Italy.
authors: Francesca
authors: F
authors: Racca
authors: Rachele Ciccocioppo, Francesca Racca, Elena Betti, Gino Roberto Corazza, Centre for the Study and Cure of Inflammatory Bowel Disease, Clinica Medica I, IRCCS San Matteo Hospital Foundation, University of Pavia, 27100 Pavia, Italy.
authors: Stefania
authors: S
authors: Paolucci
authors: Rachele Ciccocioppo, Francesca Racca, Elena Betti, Gino Roberto Corazza, Centre for the Study and Cure of Inflammatory Bowel Disease, Clinica Medica I, IRCCS San Matteo Hospital Foundation, University of Pavia, 27100 Pavia, Italy.
authors: Giulia
authors: G
authors: Campanini
authors: Rachele Ciccocioppo, Francesca Racca, Elena Betti, Gino Roberto Corazza, Centre for the Study and Cure of Inflammatory Bowel Disease, Clinica Medica I, IRCCS San Matteo Hospital Foundation, University of Pavia, 27100 Pavia, Italy.
authors: Lodovica
authors: L
authors: Pozzi
authors: Rachele Ciccocioppo, Francesca Racca, Elena Betti, Gino Roberto Corazza, Centre for the Study and Cure of Inflammatory Bowel Disease, Clinica Medica I, IRCCS San Matteo Hospital Foundation, University of Pavia, 27100 Pavia, Italy.
authors: Elena
authors: E
authors: Betti
authors: Rachele Ciccocioppo, Francesca Racca, Elena Betti, Gino Roberto Corazza, Centre for the Study and Cure of Inflammatory Bowel Disease, Clinica Medica I, IRCCS San Matteo Hospital Foundation, University of Pavia, 27100 Pavia, Italy.
authors: Roberta
authors: R
authors: Riboni
authors: Rachele Ciccocioppo, Francesca Racca, Elena Betti, Gino Roberto Corazza, Centre for the Study and Cure of Inflammatory Bowel Disease, Clinica Medica I, IRCCS San Matteo Hospital Foundation, University of Pavia, 27100 Pavia, Italy.
authors: Alessandro
authors: A
authors: Vanoli
authors: Rachele Ciccocioppo, Francesca Racca, Elena Betti, Gino Roberto Corazza, Centre for the Study and Cure of Inflammatory Bowel Disease, Clinica Medica I, IRCCS San Matteo Hospital Foundation, University of Pavia, 27100 Pavia, Italy.
authors: Fausto
authors: F
authors: Baldanti
authors: Rachele Ciccocioppo, Francesca Racca, Elena Betti, Gino Roberto Corazza, Centre for the Study and Cure of Inflammatory Bowel Disease, Clinica Medica I, IRCCS San Matteo Hospital Foundation, University of Pavia, 27100 Pavia, Italy.
authors: Gino Roberto
authors: GR
authors: Corazza
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D016022:Case-Control Studies; D003106:Colon / Q000821:virology*; D003113:Colonoscopy; D003587:Cytomegalovirus / Q000235:genetics / Q000302:isolation & purification*; D003586:Cytomegalovirus Infections / Q000175:diagnosis* / Q000628:therapy / Q000821:virology; D004279:DNA, Viral / Q000302:isolation & purification; D003937:Diagnosis, Differential; D020031:Epstein-Barr Virus Infections / Q000175:diagnosis* / Q000628:therapy / Q000821:virology; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D007150:Immunohistochemistry; D015212:Inflammatory Bowel Diseases / Q000175:diagnosis* / Q000628:therapy / Q000821:virology; D007413:Intestinal Mucosa / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009894:Opportunistic Infections / Q000175:diagnosis* / Q000628:therapy / Q000821:virology; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors; D019562:Viral Load; D055815:Young Adult
chemical_list: D004279:DNA, Viral
keywords: Inflammatory bowel disease; Quantitative real-time polymerase chain reaction; Refractory; Steroid therapy; Viral infection