Stool and Serum CMV-PCR in Diagnosing CMV Colitis

NCT ID: NCT05522283

Last Updated: 2022-09-01

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 137 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-10-01
• Study Completion Date: 2021-10-31

Brief Summary

CMV viral load detected by real-time polymerase chain reaction (PCR) in either serum or stool may be beneficial in diagnosing CMV colitis, but the data is limited. Therefore, we aimed to investigate the diagnostic performance of stool CMV-PCR, serum CMV-PCR, and their combination in diagnosing CMV colitis using tissue histopathology as the standard reference in patients with clinical suspicion of CMV colitis.

Detailed Description

The gold standard for diagnosing CMV colitis is colonoscopy with tissue biopsy. Histology by hematoxylin and eosin stain (H&E) has a high specificity of 92-100% but low sensitivity of 10-87%. Immunohistochemistry stain(IHC) increases diagnostic sensitivity to 78-93%.Tissue polymerase chain reaction assay (PCR), the method that amplifies CMV DNA, has the highest sensitivity (92-93%); however, there is no clear cut-off value to differentiate CMV bystanders from CMV colitis. Although colonoscopy is the gold standard, it is not permitted to be performed in some situations due to a high risk of procedural complications, such as in patients with profound neutropenia, thrombocytopenia, or severe illnesses. Serum CMV-PCR is a non-invasive test that detects CMV viremia, which could be associated with CMV-GI disease. However, the results of previous studies are inconsistent.

In recent years, there has been an increasing interest in stool CMV-PCR in diagnosing CMV colitis. Stool CMV-PCR is a non-invasive test that can be either qualitative or quantitative. In the first pilot study, Herfarth et al. reported stool CMV-PCR sensitivity of 83% and specificity of 93% in 19 inflammatory bowel disease patients. Since that, there have been only a few studies reporting the performance of stool CMV-PCR in diagnosing CMV colitis, and their results are inconsistent. The reported sensitivity ranges from 16.7% to 85%, and the specificity ranges from 71 to 96%. Furthermore, the diagnostic performance of combining serum and stool CMV-PCR, which could improve diagnostic performance, has not been studied. Therefore, we aimed to investigate the diagnostic performance of stool CMV-PCR, serum CMV-PCR, and their combination in diagnosing CMV colitis using tissue histopathology as the standard reference in patients with clinical suspicion of CMV colitis. In addition, we also evaluated the correlation of viral load in stool, serum, colonic tissue, and numbers of CMV-infected cells in colonic tissue.

Patients older than 18 years with clinical suspicion of CMV colitis were enrolled. The criteria for clinically suspicious of CMV colitis included: i) presence of at least one of the risk factors, including human immunodeficiency virus infection, solid organ or hematologic stem cell transplantations, hematologic malignancy, inflammatory bowel disease, taking immunosuppressive agents or chemotherapy, and critically ill with multiple comorbidities, and ii) presenting with gastrointestinal tract symptoms, including abdominal pain, gastrointestinal bleeding, diarrhea, and bowel ileus.

All participants underwent colonoscopy with tissue biopsy for both H&E stain and immunohistochemistry for CMV (IHC-CMV). Patients with the detection of either cytomegalic cells or IHC-CMV cells were diagnosed with CMV colitis. The other two pieces of colonic tissue were sent for quantitative CMV-PCR (CMV R-gene® kit, limit of detection 450 copies/ml, Biomerieux, France). Patients who could not proceed with the colonoscopy and tissue biopsy were excluded. Quantitative stool CMV-PCR (CMV R-gene® kit, limit of detection 450 copies/ml, Biomerieux, France) and quantitative serum CMV-PCR (Cobas® CMV, limit of detection 150 copies/ml, Roche, USA) were collected within seven days of colonoscopy.

Conditions

CMV Colitis

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

CMV colitis

Patients with the detection of either cytomegalic cells or IHC-CMV cells were diagnosed with CMV colitis.

Stool and blood CMV PCR

Intervention Type: DIAGNOSTIC_TEST

Quantitative stool CMV-PCR (CMV R-gene® kit, limit of detection 450 copies/ml, Biomerieux, France) and quantitative serum CMV-PCR (Cobas® CMV, limit of detection 150 copies/ml, Roche, USA) were collected within seven days of colonoscopy.

Non-CMV colitis

Symptomatic patients were not detected with either cytomegalic cells or IHC-CMV cells.

Stool and blood CMV PCR

Intervention Type: DIAGNOSTIC_TEST

Quantitative stool CMV-PCR (CMV R-gene® kit, limit of detection 450 copies/ml, Biomerieux, France) and quantitative serum CMV-PCR (Cobas® CMV, limit of detection 150 copies/ml, Roche, USA) were collected within seven days of colonoscopy.

Healthy volunteers

Asymptomatic patients underwent colonoscopy for screening.

Stool and blood CMV PCR

Intervention Type: DIAGNOSTIC_TEST

Quantitative stool CMV-PCR (CMV R-gene® kit, limit of detection 450 copies/ml, Biomerieux, France) and quantitative serum CMV-PCR (Cobas® CMV, limit of detection 150 copies/ml, Roche, USA) were collected within seven days of colonoscopy.

Interventions

Stool and blood CMV PCR

Quantitative stool CMV-PCR (CMV R-gene® kit, limit of detection 450 copies/ml, Biomerieux, France) and quantitative serum CMV-PCR (Cobas® CMV, limit of detection 150 copies/ml, Roche, USA) were collected within seven days of colonoscopy.

Intervention Type: DIAGNOSTIC_TEST

Other Intervention Names

Colonoscopy with colonic tissue biopsy

Eligibility Criteria

Inclusion Criteria

• Patients older than 18 years with clinical suspicion of CMV colitis were enrolled.

Exclusion Criteria

• Patients who could not proceed with the colonoscopy and tissue biopsy were excluded.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Mahidol University

OTHER

Sponsor Role: lead

Responsible Party

Julajak Limsrivilai

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Gastroenterology division, Faculty of Medicine, Siriraj Hospital, Mahidol University

Bangkok, , Thailand

Countries

Thailand

References

Sattayalertyanyong O, Limsrivilai J, Phaophu P, Subdee N, Horthongkham N, Pongpaibul A, Angkathunyakul N, Chayakulkeeree M, Pausawasdi N, Charatcharoenwitthaya P. Performance of Cytomegalovirus Real-Time Polymerase Chain Reaction Assays of Fecal and Plasma Specimens for Diagnosing Cytomegalovirus Colitis. Clin Transl Gastroenterol. 2023 May 1;14(5):e00574. doi: 10.14309/ctg.0000000000000574.

Reference Type: DERIVED

PMID: 36854054 (View on PubMed)

Other Identifiers

Si 810/2020

Identifier Type: -

Identifier Source: org_study_id