Prognostic Value of the Burden of Cytomegalovirus Colonic Reactivation Evaluated by Immunohistochemical Staining in Patients with Active Ulcerative Colitis

J Crohns Colitis. 2019 Mar 26;13(3):385-388. doi: 10.1093/ecco-jcc/jjy173.

Abstract

Background: Colonic cytomegalovirus [CMV] reactivation has been involved in steroid refractoriness in patients with active ulcerative colitis [UC]. The benefits of antiviral therapy in this clinical setting are still under debate, but the burden of viral reactivation has been associated with a poorer outcome in some studies. Our aim was to assess whether the burden of CMV reactivation measured by the number of viral inclusions by immunohistochemistry [IHC-CMV] is associated with a risk of colectomy.

Methods: Biopsy sets of UC patients with positive IHC-CMV were identified from the Pathology departments of three university hospitals. All biopsies were reviewed by expert pathologists, and the maximum number of IHC-CMV-positive cells in each biopsy set was re-assessed. Epidemiological and clinical features and clinical outcomes were recorded.

Results: Forty-six positive IHC-CMV cases with UC were included. At the time of CMV reactivation, 70% were receiving corticosteroids, 33% azathioprine, and 24% anti-tumour necrosis factor [TNF] agents. Thirty-two patients [70%] were treated with antiviral therapy. The median number of IHC-CMV-positive cells was 2 cells/biopsy [IQR 1-4]. Fourteen patients [30%] underwent colectomy, and 4 of them [29%] showed persistence of CMV in the surgical specimen. In the multivariate analysis, colectomy was only associated with >2 positive cells/biopsy [p = 0.048] and younger age [p = 0.023].

Conclusions: The burden of CMV colonic reactivation in patients with active UC, as measured by IHC, seems to be related to the risk of colectomy, and more data is needed to understand whether antiviral therapy guided by CMV burden will alter the clinical outcome.

Keywords: Cytomegalovirus; colectomy; ulcerative colitis.

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Adult
  • Age Factors
  • Antiviral Agents / therapeutic use
  • Azathioprine / therapeutic use
  • Colectomy*
  • Colitis, Ulcerative / complications
  • Colitis, Ulcerative / drug therapy
  • Colitis, Ulcerative / surgery*
  • Colon / pathology
  • Colon / virology*
  • Cytomegalovirus / physiology*
  • Cytomegalovirus Infections / complications
  • Cytomegalovirus Infections / drug therapy*
  • Female
  • Humans
  • Immunohistochemistry
  • Immunosuppressive Agents / therapeutic use
  • Male
  • Middle Aged
  • Prognosis
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Valganciclovir / therapeutic use
  • Virus Activation*

Substances

  • Adrenal Cortex Hormones
  • Antiviral Agents
  • Immunosuppressive Agents
  • Tumor Necrosis Factor-alpha
  • Valganciclovir
  • Azathioprine