HHV-6-DNAEMIA RELATED TO CMV-DNAEMIA AFTER LIVER TRANSPLANTATION

Abstract

O173 Aims: In addition to cytomegalovirus (CMV), activation of other betaherpesviruses, especially human herpesvirus 6 (HHV-6), have been reported in liver transplant patients. HHV-6 may cause fever, hepatitis and neurological disorders, but most activations are asymptomatic. The purpose of this study was to investigate the post transplant HHV-6-DNAenemia in relation to CMV-DNAemia in liver transplant patients. Methods: Thirty-one adult liver allograft recipients transplanted during 2002-2003 were regularly monitored for CMV and HHV-6 during the first three months after transplantation. For the diagnosis of CMV infections pp65-antigenemia assay and quantitative DNA-PCR were used, in parallel. HHV-6 was demonstrated, by using quantitative DNA-PCR and the HHV-6 antigenemia test for the both variants A and B, from the same blood specimens which were obtained for CMV monitoring. Altogether 253 blood specimens of 31 recipients analyzed were analyzed. In addition, CMV and HHV-6 specific antigens were demonstrated by immunohistochemistry in liver biopsy specimens obtained for routine histopathological examination, in the case of graft dysfunction. Results: Thirteen patients (40%) developed a clinically significant CMV infection during the first 3 months (first pp65/DNA-positive finding mean 33 days, range 5-62 days) after transplantation and were treated with intravenous ganciclovir. The peak viral loads of these symptomatic CMV infections were high (CMV-DNA 34210±37557 copies/ml plasma) and one patient even developed CMV-hepatitis. Six additional asymptomatic patients demonstrated significantly lower CMV-DNAemia levels (1020±1008 copies/ml, p<0.05), and were not treated. Concurrently with CMV, HHV-6 DNAemia and antigenemia was detected in 17/19 patients (first positive finding mean 11 days, range 6-24 days) after transplantation. Most HHV-6 cases were of variant B, but also two HHV-6A activations were recorded. HHV-6 appeared prior to CMV in most cases (12/17). However, the peak viral loads were low (HHV-6-DNA <1500 copies/ml blood), even in the 5 patients who demonstrated HHV-6 antigens in the liver biopsies. All CMV infections were successfully treated with ganciglovir and the CMV DNAemia/antigenemia subsided. HHV-6 also responded to the antiviral treatment, but more slowly and less clearly, and recurrences were common. Conclusions: HHV-6 activations were common and usually associated with CMV infection in liver transplant patients. The findings demonstrate that not only CMV but also the other betaherpesviruses may activate in transplant patients. Further investigation of the clinical significance of HHV-6 DNAemia/antigenemia is necessary.