Human cytomegalovirus and Epstein-Barr virus infection in inflammatory bowel disease:Need for mucosal viral load measurement

AIM: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 comparedto 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/105cells)than in non-refractory(HCMV 0 and EBV 6copies/105 cells;P<0.05 and<0.001)IBD patients and controls(HCMV and EBV 0 copies/105 cells;P<0.001 for both).Refractory patients showed DNA peak values≥103 copies/105 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.CONCLUSION: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.