Sitomegalovirüs Gastrointestinal Hastalığının Tanısında Plazmada CMV Virüs Yükü Eşik Değeri Elde Edilmesi, Testin Tanısal Performans Ölçütlerinin Belirlenmesi ve Hastalığı Tahmin Etmeye Yönelik Skorlama Sistemi Geliştirilmesi

Abstract

Cytomegalovirus (CMV) is a DNA virus belonging to the Herpesviridae family. In healthy individuals, CMV usually causes an asymptomatic infection or a mild illness. After primary infection, CMV remains in a latent state in tissues and organs and can be reactivated in the presence of particular circumstances, and reinfection may also occur. A more severe course of CMV infection, tissue and organ involvement can be developed in individuals with severe immunosuppression such as transplant recipients and those with acquired immunodeficiency syndrome due to the immunosuppressive medications or the disease itself. End-organ involvement is usually reported in the retina, gastrointestinal system, central nervous system, liver, and lungs. Cytomegalovirus gastrointestinal disease (CMV-GID) can involve any area of the epithelium lining the gastrointestinal tract mucosa, from the mouth to the anus. Accurate and early diagnosis is very important because it can lead to life-threatening consequences such as bleeding and perforation. The gold standard for the diagnosis of CMV-GID is demonstration of histopathological findings related to CMV in endoscopic biopsy or surgically removed tissue specimens, and confirmation of the diagnosis, if possible, by immunohistochemical examination. Difficulty or delay in diagnosis may be experienced due to the need for an invasive procedure to obtain the tissue sample; the presence of conditions that may hinder intervention in some patients; the patient's refusal to give consent for the interventional procedure; and the turnaround time for histopathological examination reports. There is a need for non-invasive and early yielding methods and approaches that can predict the diagnosis of CMV-GID with optimal diagnostic performance measures that can guide the preemptive treatment decision while pending histopathological examination results. It is emphasized that the detection of CMV viral load in plasma with polymerase chain reaction (PCR) as a method that does not require invasive procedures and can give rapid results should be used in the diagnosis of CMV-GID. In this study, demographic information, immunosuppressive medications, patient complaints, laboratory parameters, endoscopic examination findings, antiviral treatment status, and follow-up results of 125 people diagnosed with CMV-GID and 177 people who were not diagnosed with CMV-GID based on histopathological examination of tissue samples, were retrospectively evaluated. Using “Receiver Operating Characteristic” (ROC) analysis, the cut-off value for plasma CMV viral load detected by PCR which can predict the diagnosis of CMV-GID was determined; the change of this threshold in different groups in terms of the underlying disorder was established; and a scoring system was developed to predict CMV-GID. The optimal cut-off value of plasma CMV viral load for the diagnosis of CMV-GID was found to be 272 copies/mL. Separate threshold values were also obtained for each underlying medical condition. In univariate analyses, being over the age of 65; use of systemic steroids; use of azathioprine; use of more than two immunosuppressive medications; presence of ulcer, exuding ulcer, irregular ulcer, large mucosal defect, macroscopic hemorrhage, and pancolitis in endoscopic examination were determined as risk factors and findings associated with CMV-GID. A scoring system has been proposed with the model using multivariate analysis. Accordingly, 8 points for being over 65 years of age; 5 points for using systemic steroids; 9 points for erosion, 11 points for ulcer, 6 points for pancolitis, 10 points for granular appearance in endoscopic examination; 7 points for an increase of greater than 1 log10 copies/mL in plasma CMV viral load between two consecutive samples. The optimal value of the total score for predicting CMV-GID was determined as 28.1. It has been shown that patients with a diagnosis of CMV-GID have longer hospital stays and higher mortality rates than those without, and improvement in clinical signs and symptoms was significantly common in patients with a diagnosis of CMV-GID who received antiviral treatment as compared to the group that did not receive treatment. The use of the proposed scoring system and determination of plasma CMV viral load can help predict CMV-GID and facilitate early diagnosis and treatment.