The detection of the cytomegalovirus DNA in the colonic mucosa of patients with ulcerative colitis is associated with increased long-term risk of proctocolectomy: results from an outpatient IBD clinic
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Cytomegalovirus (CMV) infection has been found to be associated with a reactivation of ulcerative colitis (UC) and with an impaired response to medical therapy. In the past, only limited data were available on the long-term outcome for UC patients with positive tissue CMV-PCR in the colonic mucosa.
Between January 2010 and April 2015, we performed a qualitative PCR screening for CMV DNA in one biopsy from most actively inflamed rectal mucosa (tCMV-PCR). All tCMV-PCR-positive patients received 900 mg of valganciclovir b.i.d. for at least 15 days. We analyzed the association of the tCMV-PCR status with the time to steroid-free remission (SFR) and with the risk of proctocolectomy during the further course.
One hundred eight consecutive patients (50 women, 58 men, median age 41 years, median UC duration 6 years) with active UC not responding to anti-inflammatory medication were analyzed. Eight of the 24 tCMV-PCR-positive patients (33.3%) compared to ten of the 84 tCMV-PCR-negative patients (11.9%) underwent proctocolectomy during a median follow-up of 52 months (p < 0.005). The median time from CMV diagnosis to colectomy was 501 days (median, interquartile range (IQR): 170, 902 days) in tCMV-PCR-positive and 958 days (IQR: 287, 1328 days) in tCMV-PCR-negative patients (p < 0.01). The median time to SFR was 126 days in tCMV-PCR-positive patients vs. 63 days in tCMV-PCR-negative patients (p < 0.01).
The detection of the CMV DNA in the colonic mucosa of patients with active UC is associated with a longer time to steroid-free UC remission and with an increased rate and earlier need of proctocolectomy.
KeywordsUlcerative colitis Cytomegalovirus Proctocolectomy Polymerase chain reaction
TK, AB, PD, CK, and NT developed the standard of care, cared for all patients, and did the endoscopic biopsies. RK did the PCRs. ES did the immunohistochemistry. WS did the retrospective chart analysis and provided raw data for statistical analysis. This study is part of the doctorate thesis of WS. TB, AS, and NT conceived the study. TB and NT did the statistical analyses. AS conducted the doctorate thesis procedure of WS. All authors have read and approved the final manuscript.
Gesellschaft für Klinische Studien Leipzig, Germany.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- 2.Al-Zafiri R, Gologan A, Galiatsatos P et al (2012) Cytomegalovirus complicating inflammatory bowel disease: a 10-year experience in a community-based, university-affiliated hospital. Gastroenterol Hepatol (NY) 8:230–239Google Scholar
- 7.Roblin X, Pillet S, Oussalah A, Berthelot P, del Tedesco E, Phelip JM, Chambonnière ML, Garraud O, Peyrin-Biroulet L, Pozzetto B (2011) Cytomegalovirus load in inflamed intestinal tissue is predictive of resistance to immunosuppressive therapy in ulcerative colitis. Am J Gastroenterol 106:2001–2008CrossRefGoogle Scholar
- 9.Mowat C, Cole A, Windsor A, Ahmad T, Arnott I, Driscoll R, Mitton S, Orchard T, Rutter M, Younge L, Lees C, Ho GT, Satsangi J, Bloom S, on behalf of the IBD Section of the British Society of Gastroenterology (2011) Guidelines for the management of inflammatory bowel disease in adults. Gut 60:571–607CrossRefGoogle Scholar
- 10.Rahier JF, Magro F, Abreu C, Armuzzi A, Ben-Horin S, Chowers Y, Cottone M, de Ridder L, Doherty G, Ehehalt R, Esteve M, Katsanos K, Lees CW, Macmahon E, Moreels T, Reinisch W, Tilg H, Tremblay L, Veereman-Wauters G, Viget N, Yazdanpanah Y, Eliakim R, Colombel JF, European Crohn’s and Colitis Organisation (ECCO) (2014) Second European evidence-based consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease. J Crohns Colitis 8:443–468CrossRefGoogle Scholar
- 11.Kucharzik T, Dignass A, Atreya R, Bokemeyer B, Esters P, Herrlinger K, Kannengießer K, Kienle P, Langhorst J, Lügering A, Schreiber S, Stallmach A, Stein J, Sturm A, Teich N, Siegmund B (2018) Updated S3-guideline ulcerative colitis. German Society for Digestive and Metabolic Diseases. Z Gastroenterol 56:1087–1169Google Scholar
- 12.Matsuoka K, Iwao Y, Mori T, Sakuraba A, Yajima T, Hisamatsu T, Okamoto S, Morohoshi Y, Izumiya M, Ichikawa H, Sato T, Inoue N, Ogata H, Hibi T (2007) Cytomegalovirus is frequently reactivated and disappears without antiviral agents in ulcerative colitis patients. Am J Gastroenterol 102:331–337CrossRefGoogle Scholar
- 17.Yoshino T, Nakase H, Ueno S, Uza N, Inoue S, Mikami S, Matsuura M, Ohmori K, Sakurai T, Nagayama S, Hasegawa S, Sakai Y, Chiba T (2007) Usefulness of quantitative real-time PCR assay for early detection of cytomegalovirus infection in patients with ulcerative colitis refractory to immunosuppressive therapies. Inflamm Bowel Dis 13:1516–1521CrossRefGoogle Scholar
- 19.Lee HS, Park SH, Kim SH, Kim J, Choi J, Lee HJ, Kim WS, Lee JM, Kwak MS, Hwang SW, Yang DH, Kim KJ, Ye BD, Byeon JS, Myung SJ, Yoon YS, Yu CS, Kim JH, Yang SK (2016) Risk factors and clinical outcomes associated with cytomegalovirus colitis in patients with acute severe ulcerative colitis. Inflamm Bowel Dis 22:912–918CrossRefGoogle Scholar
- 25.Kopylov U, Papamichael K, Katsanos K, Waterman M, Bar-Gil Shitrit A, Boysen T, Portela F, Peixoto A, Szilagyi A, Silva M, Maconi G, Har-Noy O, Bossuyt P, Mantzaris G, Barreiro de Acosta M, Chaparro M, Christodoulou DK, Eliakim R, Rahier JF, Magro F, Drobne D, Ferrante M, Sonnenberg E, Siegmund B, Muls V, Thurm T, Yanai H, Dotan I, Raine T, Levin A, Israeli E, Ghalim F, Carbonnel F, Vermeire S, Ben-Horin S, Roblin X (2017) Impact of infliximab and cyclosporine on the risk of colectomy in hospitalized patients with ulcerative colitis complicated by cytomegalovirus-a multicenter retrospective study. Inflamm Bowel Dis 23(9):1605–1613Google Scholar