International Journal of Colorectal Disease

, Volume 34, Issue 3, pp 393–400 | Cite as

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

  • Wiebke Schenk
  • Tobias Klugmann
  • Annett Borkenhagen
  • Chris Klecker
  • Peter Dietel
  • Ralf Kirschner
  • Eckhardt Schneider
  • Tony Bruns
  • Andreas Stallmach
  • Niels TeichEmail author
Original Article



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.


Ulcerative colitis Cytomegalovirus Proctocolectomy Polymerase chain reaction 


Authors’ contributions

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.


  1. 1.
    Lv YL, Han FF, Jia YJ, Wan ZR, Gong LL, Liu H, Liu LH (2017) Is cytomegalovirus infection related to inflammatory bowel disease, especially steroid-resistant inflammatory bowel disease? A meta-analysis. Infect Drug Resist 10:511–519CrossRefGoogle Scholar
  2. 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
  3. 3.
    Inokuchi T, Kato J, Hiraoka S, Suzuki H, Nakarai A, Hirakawa T, Akita M, Takahashi S, Harada K, Okada H, Yamamoto K (2014) Long-term follow-up of ulcerative colitis patients treated on the basis of their cytomegalovirus antigen status. World J Gastroenterol 20:509–517CrossRefGoogle Scholar
  4. 4.
    Zhang C, Krishna SG, Hinton A, Arsenescu R, Levine EJ, Conwell DL (2016) Cytomegalovirus-related hospitalization is associated with adverse outcomes and increased healthcare resource utilization in inflammatory bowel disease. Clin Transl Gastroenterol 7:e150CrossRefGoogle Scholar
  5. 5.
    Kishore J (2004) Infection with cytomegalovirus in patients with inflammatory bowel disease: prevalence, clinical significance and outcome. J Med Microbiol 53:1155–1160CrossRefGoogle Scholar
  6. 6.
    Maconi G, Lombardini M, Furfaro F, Bezzio C, Zerbi P, Ardizzone S (2014) Long-term outcome of inflammatory bowel diseases with cytomegalovirus colitis: effect of antiviral treatment. Eur J Gastroenterol Hepatol 26:1146–1151CrossRefGoogle Scholar
  7. 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
  8. 8.
    Shukla T, Singh S, Loftus EV Jr, Bruining DH, McCurdy JD (2015) Antiviral therapy in steroid-refractory ulcerative colitis with cytomegalovirus: systematic review and meta-analysis. Inflamm Bowel Dis 21:2718–2725CrossRefGoogle Scholar
  9. 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. 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. 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. 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
  13. 13.
    Lawlor G, Moss AC (2010) Cytomegalovirus in inflammatory bowel disease: pathogen or innocent bystander? Inflamm Bowel Dis 16:1620–1627CrossRefGoogle Scholar
  14. 14.
    Pillet S, Pozzetto B, Roblin X (2016) Cytomegalovirus and ulcerative colitis: place of antiviral therapy. World J Gastroenterol 22:2030–2045CrossRefGoogle Scholar
  15. 15.
    Kotton CN, Kumar D, Caliendo AM et al (2010) Transplantation Society International CMV Consensus Group. International consensus guidelines on the management of cytomegalovirus in solid organ transplantation. Transplantation 89:779–795CrossRefGoogle Scholar
  16. 16.
    Ganzenmueller T, Henke-Gendo C, Schlué J et al (2009) Quantification of cytomegalovirus DNA levels in intestinal biopsies as a diagnostic tool for CMV intestinal disease. J Clin Virol 46:254–258CrossRefGoogle Scholar
  17. 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
  18. 18.
    Okahara K, Nagata N, Shimada T, Joya A, Hayashida T, Gatanaga H, Oka S, Sakurai T, Uemura N, Akiyama J (2017) Colonic cytomegalovirus detection by mucosal PCR and antiviral therapy in ulcerative colitis. PLoS One 12:e0183951CrossRefGoogle Scholar
  19. 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
  20. 20.
    Johnson J, Affolter K, Boynton K, Chen X, Valentine J, Peterson K (2018) CMV disease in IBD: comparison of diagnostic tests and correlation with disease outcome. Inflamm Bowel Dis 24:1539–1546CrossRefGoogle Scholar
  21. 21.
    Levin A, Yaari S, Stoff R, Caplan O, Wolf DG, Israeli E (2017) Diagnosis of cytomegalovirus infection during exacerbation of ulcerative colitis. Digestion 96:142–148CrossRefGoogle Scholar
  22. 22.
    Tandon P, James P, Cordeiro E, Mallick R, Shukla T, McCurdy JD (2017) Diagnostic accuracy of blood-based tests and histopathology for cytomegalovirus reactivation in inflammatory bowel disease: a systematic review and meta-analysis. Inflamm Bowel Dis 23:551–560CrossRefGoogle Scholar
  23. 23.
    Zagórowicz E, Bugajski M, Wieszczy P et al (2016) Cytomegalovirus infection in ulcerative colitis is related to severe inflammation and a high count of cytomegalovirus-positive cells in biopsy is a risk factor for colectomy. J Crohns Colitis 10:1205–1211CrossRefGoogle Scholar
  24. 24.
    Zagórowicz E, Przybysz A, Szlak J, Magdziak A, Wieszczy P, Mróz A (2018) Detection of cytomegalovirus by immunohistochemistry of colonic biopsies and quantitative blood polymerase chain reaction: evaluation of agreement in ulcerative colitis. Scand J Gastroenterol 53:435–441CrossRefGoogle Scholar
  25. 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
  26. 26.
    McCurdy JD, Enders FT, Jones A et al (2015) Detection of cytomegalovirus in patients with inflammatory bowel disease: where to biopsy and how many biopsies? Inflamm Bowel Dis 21:2833–2838CrossRefGoogle Scholar
  27. 27.
    Thörn M, Rorsman F, Rönnblom A, Sangfelt P, Wanders A, Eriksson BM, Bondeson K (2016) Active cytomegalovirus infection diagnosed by real-time PCR in patients with inflammatory bowel disease: a prospective, controlled observational study. Scand J Gastroenterol 51:1075–1080CrossRefGoogle Scholar
  28. 28.
    Wu XW, Yang MF, Li N, Wang FY (2015) Unfavorable outcome of antiviral therapy in cytomegalovirus-positive ulcerative colitis may be due to inappropriate study inclusion in meta-analysis. World J Gastroenterol 21:1689–1690CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Wiebke Schenk
    • 1
    • 2
  • Tobias Klugmann
    • 1
  • Annett Borkenhagen
    • 1
  • Chris Klecker
    • 1
  • Peter Dietel
    • 1
  • Ralf Kirschner
    • 3
  • Eckhardt Schneider
    • 4
  • Tony Bruns
    • 2
  • Andreas Stallmach
    • 2
  • Niels Teich
    • 1
    • 5
    Email author
  1. 1.Internistische Gemeinschaftspraxis für Verdauungs- und Stoffwechselkrankheiten, Leipzig und SchkeuditzLeipzigGermany
  2. 2.Klinik für Innere Medizin IVUniversitätsklinikum JenaJenaGermany
  3. 3.MVZ Labor Dr. Reising-Ackermann und KollegenLeipzigGermany
  4. 4.Gemeinschaftspraxis für PathologieLeipzigGermany
  5. 5.Medizinische Fakultät der Friedrich-Schiller-Universität JenaJenaGermany

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