Intest Res.  2021 Oct;19(4):438-447. 10.5217/ir.2020.00055.

High mucosal cytomegalovirus DNA helps predict adverse short-term outcome in acute severe ulcerative colitis

Affiliations
  • 1Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
  • 2Department of Microbiology, All India Institute of Medical Sciences, New Delhi, India
  • 3Department of Gastrointestinal Surgery, All India Institute of Medical Sciences, New Delhi, India
  • 4Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
  • 5Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, India
  • 6Translational Gastroenterology Unit, NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, UK

Abstract

Background/Aims
Predictors of short-term outcome of intravenous (IV) steroid therapy in acute severe ulcerative colitis (ASUC) have been well described, but the impact of cytomegalovirus (CMV) infection as a predictor of outcome remains debatable. We investigated the role of quantitative CMV polymerase chain reaction (PCR) as a predictor of short-term outcome in patients with ASUC.
Methods
Consecutive patients with ASUC satisfying Truelove and Witts criteria hospitalized at All India Institute of Medical Sciences (AIIMS) from May 2016 to July 2019 were included; all received IV steroid. The primary outcome measure was steroid-failure defined as the need for rescue therapy (with ciclosporin or infliximab) or colectomy during admission. AIIMS’ index (ulcerative colitis index of severity > 6 at day 1+fecal calprotectin > 1,000 μg/g at day 3), with quantitative CMV PCR on biopsy samples obtained at initial sigmoidoscopy were correlated with the primary outcome.
Results
Thirty of 76 patients (39%) failed IV corticosteroids and 12 (16%) underwent surgery. Patients with steroid failure had a significantly higher mucosal CMV DNA than responders (3,454 copies/mg [0–2,700,000] vs. 116 copies/mg [0–27,220]; P< 0.01). On multivariable analysis, mucosal CMV DNA load > 2,000 copies/mg (odds ratio [OR], 10.2; 95% confidence interval [CI], 2.6–39.7; P< 0.01) and AIIMS’ index (OR, 39.8; 95% CI, 4.4–364.4; P< 0.01) were independent predictors of steroid-failure and need for colectomy. The combination correctly predicted outcomes in 84% of patients with ASUC.
Conclusions
High mucosal CMV DNA ( > 2,000 copies/mg) independently predicts failure of IV corticosteroids and short-term risk of colectomy and it has an additional value to the established markers of disease severity in patients with ASUC.

Keyword

Colitis ulcerative; Steroid failure; Prediction; Cytomegalovirus

Figure

  • Fig. 1 CONSORT diagram: study population. ASC, acute severe colitis.

  • Fig. 2 Receiver operating curve of mucosal quantitative cytomegalovirus polymerase chain reaction for prediction of steroid failure in acute severe ulcerative colitis (ASUC) with an area under the curve of 74% (95% confidence interval, 61–87). A cutoff of 2,000 copies/mg had a sensitivity of 67% and specificity of 70% for prediction of steroid failure in ASUC.

  • Fig. 3 Prediction of steroid response in acute severe ulcerative colitis (ASUC) patients using All India Institute of Medical Sciences index and high mucosal cytomegalovirus DNA load (>2,000 copies/mg).


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