Diagnostic utility of quantitative cytomegalovirus DNA polymerase chain reaction in intestinal biopsies from patients with inflammatory bowel disease

Abstract

OBJECTIVES: Diagnostic utility of cytomegalovirus (CMV) DNA quantitative polymerase chain reaction (qPCR) in inflammatory bowel disease (IBD) has not been established. We aimed to compare diagnostic utility of qPCR for CMV in biopsy specimens with blood, serology, and histopathology.

MATERIALS AND METHODS: A total of 132 patients were included (92 ulcerative colitis [UC], 9 Crohn's disease, and 31 unclassified IBD). Comparison between CMV IgM, CMV DNA qPCR in biopsy, in blood and histopathology was done. Positive result in any of the test was considered as CMV infection. Various risk factors for CMV association with IBD were analyzed.

RESULTS: Confirmed CMV infection was seen in 41 (31.1%) patients. Diagnostic sensitivity of different assays was: DNA in biopsy seen in 37 (90.2%), DNA in blood in 19 (46.3%), CMV IgM in 15 (36.5%), and histopathology in 8 (19.5%). Thirty-two UC cases were further followed up for a median time of 14.0 (R: 3–31) months. They were grouped as group I – biopsy and blood DNA both positive (14, 43.7%), Group II – biopsy positive and blood negative (17, 53.1%), and Group III – biopsy negative but blood positive (1, 3.1%). CMV DNA viral load in Group I was significantly higher (mean: 4.2 ± 1.0 log₁₀ copies/mg) than Group II (mean: 3.2 ± 0.6 copies/mg) and Group III (viral load: 2.69 log₁₀ copies/ml), P < 0.001. Steroid refractoriness was seen more in Group I cases (n = 9) P < 0.001. A cutoff of ≥2.5 log₁₀ copies/mg of DNA in tissue was predictive for steroid refractoriness (AUROC = 0.84).

CONCLUSIONS: Quantitation of CMV DNA in intestinal biopsy is a useful diagnostic tool and can predict response to steroid treatment in patients with UC.

Key words

Cytomegalovirus - inflammatory bowel disease - quantitative polymerase chain reaction - ulcerative colitis

Publication History

Received: 23 May 2017

Accepted: 12 July 2017

Article published online:
19 February 2020

• References

• 1 Christidou A, Zambeli E, Mantzaris G. Cytomegalovirus and inflammatory bowel disease: Pathogenicity, diagnosis and treatment. Ann Gastroenterol 2007;20:110-5.
• 2 Sager K, Alam S, Bond A, Chinnappan L, Probert CS. Review article: Cytomegalovirus and inflammatory bowel disease. Aliment Pharmacol Ther 2015;41:725-33.
• 3 Powell RD, Warner NE, Levine RS, Kirsner JB. Cytomegalic inclusion disease and ulcerative colitis; report of a case in a young adult. Am J Med 1961;30:334-40.
• 4 Kandiel A, Lashner B. Cytomegalovirus colitis complicating inflammatory bowel disease. Am J Gastroenterol 2006;101:2857-65.
• 5 Pillet S, Pozzetto B, Jarlot C, Paul S, Roblin X. Management of cytomegalovirus infection in inflammatory bowel diseases. Dig Liver Dis 2012;44:541-8.
• 6 Roblin X, Pillet S, Oussalah A, Berthelot P, Del Tedesco E, Phelip JM, et al. Cytomegalovirus load in inflamed intestinal tissue is predictive of resistance to immunosuppressive therapy in ulcerative colitis. Am J Gastroenterol 2011;106:2001-8.
• 7 Cottone M, Pietrosi G, Martorana G, Casà A, Pecoraro G, Oliva L, et al. Prevalence of cytomegalovirus infection in severe refractory ulcerative and Crohn's colitis. Am J Gastroenterol 2001;96:773-5.
• 8 Pillet S, Pozzetto B, Roblin X. Cytomegalovirus and ulcerative colitis: Place of antiviral therapy. World J Gastroenterol 2016;22:2030-45.
• 9 Kishore J, Ghoshal U, Ghoshal UC, Krishnani N, Kumar S, Singh M, et al. Infection with cytomegalovirus in patients with inflammatory bowel disease: Prevalence, clinical significance and outcome. J Med Microbiol 2004;53:1155-60.
• 10 Rahier JF, Magro F, Abreu C, Armuzzi A, Ben-Horin S, Chowers Y, et al. Second European evidence-based consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease. J Crohns Colitis 2014;8:443-68.
• 11 Kou T, Nakase H, Tamaki H, Kudo T, Nishio A, Chiba T, et al. Cytomegalovirus infection in patients with ulcerative colitis diagnosed by quantitative real-time PCR analysis. Dig Dis Sci 2006;51:1052-5.
• 12 Kuwabara A, Okamoto H, Suda T, Ajioka Y, Hatakeyama K. Clinicopathologic characteristics of clinically relevant cytomegalovirus infection in inflammatory bowel disease. J Gastroenterol 2007;42:823-9.
• 13 Garrido E, Carrera E, Manzano R, Lopez-Sanroman A. Clinical significance of cytomegalovirus infection in patients with inflammatory bowel disease. World J Gastroenterol 2013;19:17-25.
• 14 Kim YS, Kim YH, Kim JS, Cheon JH, Ye BD, Jung SA, et al. The prevalence and efficacy of ganciclovir on steroid-refractory ulcerative colitis with cytomegalovirus infection: A prospective multicenter study. J Clin Gastroenterol 2012;46:51-6.
• 15 Ormeci AC, Akyuz F, Baran B, Soyer OM, Gokturk S, Onel M, et al. Steroid-refractory inflammatory bowel disease is a risk factor for CMV infection. Eur Rev Med Pharmacol Sci 2016;20:858-65.
• 16 Beaugerie L, Cywiner-Golenzer C, Monfort L, Girard PM, Carbonnel F, Ngô Y, et al. Definition and diagnosis of cytomegalovirus colitis in patients infected by human immunodeficiency virus. J Acquir Immune Defic Syndr Hum Retrovirol 1997;14:423-9.
• 17 Yoshino T, Nakase H, Ueno S, Uza N, Inoue S, Mikami S, et al. 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 2007;13:1516-21.
• 18 Hommes DW, Sterringa G, van Deventer SJ, Tytgat GN, Weel J. The pathogenicity of cytomegalovirus in inflammatory bowel disease: A systematic review and evidence-based recommendations for future research. Inflamm Bowel Dis 2004;10:245-50.
• 19 Matsuoka K, Iwao Y, Mori T, Sakuraba A, Yajima T, Hisamatsu T, et al. Cytomegalovirus is frequently reactivated and disappears without antiviral agents in ulcerative colitis patients. Am J Gastroenterol 2007;102:331-7.
• 20 Criscuoli V, Rizzuto MR, Montalbano L, Gallo E, Cottone M. Natural history of cytomegalovirus infection in a series of patients diagnosed with moderate-severe ulcerative colitis. World J Gastroenterol 2011;17:633-8.
• 21 Berk T, Gordon SJ, Choi HY, Cooper HS. Cytomegalovirus infection of the colon: A possible role in exacerbations of inflammatory bowel disease. Am J Gastroenterol 1985;80:355-60.
• 22 Page MJ, Dreese JC, Poritz LS, Koltun WA. Cytomegalovirus enteritis: A highly lethal condition requiring early detection and intervention. Dis Colon Rectum 1998;41:619-23.
• 23 Yee YK, Wong SW, Szeto ML. Ulcerative colitis exacerbation associated with cytomegalovirus infection. Hong Kong Med J 1998;4:437-39.
• 24 Criscuoli V, Casà A, Orlando A, Pecoraro G, Oliva L, Traina M, et al. Severe acute colitis associated with CMV: A prevalence study. Dig Liver Dis 2004;36:818-20.
• 25 Maconi G, Colombo E, Zerbi P, Sampietro GM, Fociani P, Bosani M, et al. Prevalence, detection rate and outcome of cytomegalovirus infection in ulcerative colitis patients requiring colonic resection. Dig Liver Dis 2005;37:418-23.
• 26 Wada Y, Matsui T, Matake H, Sakurai T, Yamamoto J, Kikuchi Y, et al. Intractable ulcerative colitis caused by cytomegalovirus infection: A prospective study on prevalence, diagnosis, and treatment. Dis Colon Rectum 2003;46:S59-65.
• 27 Domènech E, Vega R, Ojanguren I, Hernández A, Garcia-Planella E, Bernal I, et al. Cytomegalovirus infection in ulcerative colitis: A prospective, comparative study on prevalence and diagnostic strategy. Inflamm Bowel Dis 2008;14:1373-9.