The pathogenesis of hepatitis C virus is influenced by cytomegalovirus.

We investigated the effect of beta-herpesviruses on allograft failure and mortality, hepatitis C virus (HCV) replication, and liver histologic characteristics among 92 HCV-infected liver transplant recipients. Reactivation of cytomegalovirus (CMV) but not of human herpesvirus 6 (HHV-6) was independently associated with allograft failure and mortality (risk ratio, 3.71; 95% confidence interval, 1.64-8.39); allograft failure and mortality was observed in 48% of patients with CMV disease, 35% of patients with subclinical CMV infection, and 17% of patients without CMV infection (P=.0275). CMV reactivation was highly predictive of mortality (P<.001), regardless of whether it remained subclinical or evolved into CMV disease. Patients with CMV disease had a higher fibrosis stage (P=.05) and had a trend toward a higher hepatitis activity index (P=.10) and HCV load (P=.10) at 16 weeks after liver transplantation. The pathogenesis of HCV is influenced by its interaction with CMV but not with HHV-6.

The clinical use of various blood compartments for cytomegalovirus (CMV) DNA quantitation in transplant recipients with CMV disease.

BACKGROUND: The quantitation of cytomegalovirus (CMV) DNA is a cornerstone in the management of CMV disease in transplant recipients. However, a consensus as to what is the optimal blood compartment for the detection and quantitation of CMV DNA in peripheral blood is nonexistent. METHODS: With an automated quantitative assay, we have simultaneously quantified the CMV DNA load in whole blood (WB), plasma (PL), peripheral blood leukocytes (PBL), and peripheral blood mononuclear cells (PBMC) in 319 samples from 17 transplant recipients with 19 episodes of CMV disease that were treated with 2 weeks of intravenous ganciclovir. RESULTS: Higher levels of CMV DNA were observed in WB than PL (PL minus WB mean difference, 0.67 log; 95% confidence interval, -1.02 to -0.32; P=0.0009). This observation was most evident before treatment with intravenous ganciclovir (pretreatment geometric mean CMV DNA was 45,412 copies per ml of WB vs. 14,995 copies per ml of PL). In contrast, the CMV DNA levels between PBL and PBMC were highly comparable throughout the course of CMV disease and its treatment. Intravenous ganciclovir exerted a uniform effect on the four blood compartments with no statistically significant difference in the degree and rate of CMV DNA decline between WB and PL and between PBL and PBMC. CONCLUSIONS: Although our study demonstrates the adequacy of all blood compartments for CMV DNA quantification, the higher sensitivity of WB and its yield of higher CMV DNA render it an optimal sample for monitoring CMV DNA load during CMV disease in immunocompromised patients.

Detection of simultaneous beta-herpesvirus infections in clinical syndromes due to defined cytomegalovirus infection.

Human herpesvirus (HHV)-6 and HHV-7 are increasingly being recognized as emerging pathogens among transplant recipients. Using quantitative polymerase chain reaction assays, we demonstrate the presence of HHV-6 and/or HHV-7 in 18 of 20 episodes of clinically presumed or microbiologically confirmed cytomegalovirus (CMV) infection. Seventeen (89%) of 19 microbiologically confirmed cytomegalovirus (CMV)-infected patients had concomitant HHV-6 variant B (47%) and/or HHV-7 (63%) infection. The degree of HHV-6 coinfection was significantly correlated with hyperbilirubinemia while HHV-7 coinfection demonstrated a non-significant trend toward cytopenias. In one of the 20 episodes described herein, the 'viral syndrome' was due solely to HHV-7 infection; clinical and virological response was observed during intravenous ganciclovir therapy in this patient. While this study emphasizes the significance of HHV-6 and/or HHV-7 coinfection during episodes of CMV infection, it significantly highlights the novel observation of the causal role of HHV-7 (in the absence of HHV-6 and CMV) in a clinical illness presumed to be caused CMV. Thus, HHV-7 (and HHV-6) should be considered as a pathogen (or copathogen) in the viral syndromes following organ transplantation.