Hepatitis C virus (HCV) has been proposed to have immunomodulatory effects in transplant recipients and may promote herpesvirus reactivation. To assess this, we compared the incidence of herpesvirus reactivation in HCV-positive and HCVnegative liver transplant recipients. Quantitative viral load testing was performed at regular intervals posttransplantation for cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesviruses (HHV) 6, 7, and 8, and varicella zoster virus (VZV) in 177 liver transplant patients who were HCV-positive (n ϭ 60) or HCV-negative (n ϭ 117). The incidence of CMV disease, CMV viremia, and the peak CMV viral load was not significantly different in HCV-positive vs. HCV-negative patients. Similarly, no differences in HHV-6 or EBV reactivation were observed. HHV-8 or VZV viremia was not detected in any patient in the study. A lower incidence of HHV-7 infection occurred in HCV-positive patients vs. HCV-negative patients (47.6% vs. 72.7%; P ϭ 0.006). In conclusion, these results suggest that HCV infection does not appear to promote herpesvirus reactivation after liver transplantation. Liver Transpl 13:1422Transpl 13: -1427Transpl 13: , 2007. © 2007 AASLD.Received February 19, 2007; accepted June 3, 2007. Cirrhosis caused by hepatitis C virus (HCV) infection is the leading indication for liver transplantation 1,2 and HCV viremia persists in up to 95% of patients posttransplantation. 3 By 5 yr posttransplantation, HCVinduced hepatitis and cirrhosis occur in approximately 80% and 10% of patients, respectively. 4,5 Herpesvirus reactivation is common after liver transplantation. Cytomegalovirus (CMV) infection and disease is especially common in CMV donor seropositive/recipient seronegative transplant recipients. Other herpesviruses, including human herpesviruses (HHV)-6 and HHV-7, also commonly reactivate after transplantation and coinfections with these viruses may manifest as febrile syndromes. 6 The interaction between herpesviruses and HCV has been proposed to be clinically important in HCV-infected liver transplant recipients. 7-10 CMV in particular may have immunomodulatory effects, and lead to cytokine dysregulation, resulting in a number of indirect effects such as an increased risk of opportunistic infection, posttransplantation lymphoproliferative disease (PTLD), and acute and chronic graft injury. 11 CMV 7 and HHV-6 7,9 have also been associated with more severe forms of HCV recurrence. Although fewer data are available, other immunomodulatory effects have also been proposed for other -herpesviruses, including It is less clear whether HCV can promote herpes viralAbbreviations: HCV, hepatitis C virus; CMV, cytomegalovirus; EBV, Epstein-Barr virus; HHV, human herpesvirus; VZV, varicella zoster virus; PTLD, posttransplantation lymphoproliferative disease.