Detection of Cytomegalovirus DNA in Plasma as an Adjunct Diagnostic for Gastrointestinal Tract Disease in Kidney and Liver Transplant Recipients

TLDR: Plasma CMV qPCR had good sensitivity and excellent specificity for CMV GI tract disease in kidney and liver transplant recipients, and variation in assay performance according to host serostatus may reflect differences in disease pathogenesis.

Abstract: (See the Editorial Commentary by Ison on pages 1560–1.) Cytomegalovirus (CMV) infection and disease are common in solid organ transplant (SOT) recipients [1], even with antiviral prophylaxis [2–4]. CMV infection is defined as viral replication without symptoms. CMV disease refers to viral replication with symptomatic illness [5, 6] and is categorized as (1) CMV syndrome with fever, malaise, and abnormal findings, such as leukopenia or thrombocytopenia, or (2) tissue-invasive disease with end-organ damage from the virus [6]. Tissue-invasive disease most commonly affects the gastrointestinal (GI) tract, resulting in esophagitis, gastritis, enteritis, or colitis [7]. Proven CMV GI tract disease requires a biopsy obtained by esophagogastroduodenoscopy and/or colonoscopy with histologic or culture-based evidence of CMV [5]. Noninvasive molecular tests have advanced our understanding of this clinical entity and affected outcomes [8]. Detection and quantification of CMV pp65 antigen or CMV DNA in blood with quantitative polymerase chain reaction assays (qPCR) are used. However, the utility of qPCR for CMV DNA in plasma as an adjunct diagnostic for CMV GI tract disease in SOT recipients has not been well described. Findings of recent studies suggest that plasma CMV DNA is frequently not detected in cases of CMV GI tract disease. In one small study (11 SOT recipients with tissue-invasive CMV disease), qPCR sensitivity was 73%, though the number of cases of GI tract disease was not specified [9]. In a larger retrospective study of a mixed cohort (immunocompetent patients, SOT recipients, and stem cell transplant recipients), the sensitivity of plasma qPCR for CMV GI tract disease was 48% based on results from 29 patients; the sensitivity in SOT recipients was not specified [10]. Finally, Grim et al [11] reported on 12 cases of CMV GI tract disease in SOT recipients; 4 (50%) of 8 patients had detectable plasma CMV DNA. Given the limited data in SOT recipients, we reviewed a large cohort of kidney and liver transplant recipients at our institution to determine the sensitivity and specificity of qPCR for plasma CMV DNA as an adjunct in the diagnosis of CMV GI tract disease.