Quantification of cytomegalovirus DNA levels in intestinal biopsies as a diagnostic tool for CMV intestinal disease

Background: CMV intestinal disease (CMV-ID) is a serious complication in immunocompromised patients and mainly diagnosed by clinical, endoscopic and histopathologic findings, whereas qualitative CMV-PCR in tissue samples is not recommended for diagnosis due to its low positive predictive value (PPV). Objectives: To study the interpretation and diagnostic use of CMV-quantification by PCR in intestinal tissue biopsies to recognize CMV-ID. To develop cut-off intestinal CMV-loads attributing illness to CMV. Study design: CMV-genome copies in 163 biopsies from the lower intestinal tract of immunocompromised patients were determined by quantitative real-time PCR, normalized to the cell number, and retrospectively compared to histopathological analysis, clinical findings and occurrence of CMV-antigenemia. Two cut-off intestinal CMV-loads, cut-off(histo) and cut-off(clin), were defined using histopathological or clinical criteria as gold standard, respectively. Results: CMV was detected in 32.5% of biopsies with a more than six log range of CMV-concentrations (1 x 10(-4)-1.4 x 10(2) copies/cell). Notably, biopsies with histopathologically or clinically confirmed CMV-ID had a significantly higher CMV-load (p < 0.001). Cut-off(histo) and cut-off(clin) were defined at the intestinal CMV-Ioad of 0.14 and 0.01 copies/cell, respectively, and improved the PPV. However, cut-off(histo) showed a decreased sensitivity for clinically defined CMV-ID cases. Interestingly, many patients with CMV-ID showed no concomitant CMV-antigenemia, suggesting a localized intestinal CMV-replication. Conclusions: Quantification of CMV in intestinal biopsies is a useful diagnostic tool allowing the definition of cut-off values that can predict CMV-ID more accurate than qualitative PCR results. Further prospective studies have to clarify wether these cut-offs can improve diagnostics and treatment of CMV-ID in day-to-day clinical practice. (C) 2009 Elsevier B.V. All rights reserved.