Clinical Features, Endoscopic Findings, and Predictive Factors for Mortality in Tissue-Invasive Gastrointestinal Cytomegalovirus Disease between Immunocompetent and Immunocompromised Patients

Abstract

Background and Aims. Tissue-invasive gastrointestinal cytomegalovirus (TI-GI CMV) disease is common in immunocompromised patients, but the increasing prevalence in immunocompetent patients has been reported. This study compared the clinical manifestations, endoscopic features, treatment outcomes, and predictors for inhospital mortality of TI-GI CMV between immunocompromised and immunocompetent patients. Methods. Patients with HIV infection, malignancy, or receiving immunosuppressive agents (chemotherapy, high dose, or long-term corticosteroids) were defined as the immunocompromised group. Demographic and inhospital mortality data were obtained and retrospectively analyzed. Results. A total of 213 patients (89 immunocompetent) with histologically confirmed TI-GI CMV were enrolled. Immunocompetent patients were older (70 vs. 52 years; p < 0.001 ), had more GI bleeding as a presenting symptom (47.2% vs. 29.0%; p = 0.010 ), and shorter symptom onset (2 vs. 14 days, p = 0.018 ). Concomitant extra-GI involvement was only seen in the immunocompromised group (6.5% vs. 0%; p = 0.02 ). Diffuse GI tract (14.5% vs. 4.5%; p = 0.032 ) and esophageal involvement (14.5% vs. 5.6%; p = 0.046 ) were more frequent in the immunocompromised, while small bowel involvement was more frequent in the immunocompetent group (19.1% vs. 8.1%; p = 0.029 ). An overall inhospital mortality was 27.7%. There was no significant difference in inhospital survival probability between the two groups (Peto-Peto test, p = 0.65 ). ICU admission (hazard ratio [HR] 7.21; 95% CI 2.55-20.36), sepsis or shock (HR 1.98; 95% CI 1.08-3.66), malnutrition (HR 2.62; 95% CI 1.05-7.01), and receiving chemotherapy (HR 5.2; 95% CI 1.89-14.29) were independent factors for inhospital mortality. Antiviral treatment for more than 14 days was the only protective factor to improve survival (Peto-Peto test, p < 0.001 ). Conclusions. Immunocompetent and immunocompromised patients with TI-GI CMV disease had distinct clinical and endoscopic characteristics. There was no significant difference in the inhospital mortality between the two groups. The factors for mortality were ICU admission, sepsis/shock, malnutrition, and receiving chemotherapy. Early diagnosis and initiation of antiviral treatment might improve the survival probability.

Cytomegalovirus Diseases of the Gastrointestinal Tract

“…In host status, old age, immunocompromised status, and malnutrition (hypoalbuminemia) resulted in impaired immune function and then poor survival. In two prior studies, old age and malnutrition were noted as negative predictive factors for mortality as well [7,9]. Since hypoalbuminemia indicates malnourishment, poor immunity, and worse tissue healing, it is responsible for increased mortality rates in several diseases, especially in patients in the ICU setting [25][26][27].…”

“…With regard to immunocompromised status, Wetwittayakhlang et al reported no significant difference in in-hospital survival, while Chaemsupaphan et al noted that the six-month mortality was higher in immunocompetent patients. These discrepant results might be associated with differences in patient selection (IHC staining, definition of immunocompromised status), study endpoints (disease-specific mortality or overall mortality), and treatment strategies [7,9]. Second, thrombocytopenia and GI bleeding were negative predictors of in-hospital mortality.…”

“…CMV diseases, regardless of the end organs, are traditionally considered an infection primarily for immunocompromised patients. However, cohort studies of the GI tract in the past decades have composed a proportion of 25-50% of immunocompetent hosts [7,9,16]. Old age, critical illness, diabetes mellitus, chronic kidney disease, end-stage renal disease, and other comorbidities can lead to immune deficiency and increase the risk of CMV diseases [16][17][18].…”

“…However, IHC staining has a higher sensitivity and specificity than routine HE staining [5,6]. Emerging research has shown that CMV diseases involved both immunocompromised and immunocompetent hosts [2,[7][8][9]. The whole alimentary tract can be infected, but leading sites are the colon and esophagus [10].…”

“…In adult patients with cancer, Ko et al noted that male sex, low body mass index, lymphopenia, hematological malignancy, steroid use, and red blood cell transfusion within a month prior to the CMV disease diagnosis were independent risk factors for the development of CMV GI disease [13]. The two latest retrospective studies that enrolled 213 and 173 patients with positive H&E or IHC staining in Thailand found that antiviral treatment was the only protective factor that improved patient survival [7,9]. However, in our previous studies on CMV gastritis, enteritis, and colitis, antiviral therapy had no significant impact on in-hospital survival [8,14,15].…”