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

BackgroundCMV 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).ObjectivesTo 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 designCMV-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-offhisto and cut-offclin, were defined using histopathological or clinical criteria as gold standard, respectively.ResultsCMV was detected in 32.5% of biopsies with a more than six log range of CMV-concentrations (1 × 10−4–1.4 × 102 copies/cell). Notably, biopsies with histopathologically or clinically confirmed CMV-ID had a significantly higher CMV-load (p < 0.001). Cut-offhisto and cut-offclin were defined at the intestinal CMV-load of 0.14 and 0.01 copies/cell, respectively, and improved the PPV. However, cut-offhisto 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.ConclusionsQuantification 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.