The Pathogenesis of Hepatitis C Virus Is Influenced by Cytomegalovirus

Abstract

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.

Human herpesvirus 6 infection in adult living related liver transplant recipients

“…It has been demonstrated that CMV infection is associated with an increased risk of recurrent HCV hepatitis after transplantation. 41,42 As HHV-6 is similar biologically to CMV, HHV-6 infection might also be implicated in HCV recurrence after liver transplant. The present analysis suggests that HHV-6 is not involved in recurrence of HCV hepatitis after liver transplantation.…”

An assessment of interactions between hepatitis C virus and herpesvirus reactivation in liver transplant recipients using molecular surveillance

“…Patients with CMV disease had a higher fibrosis stage and had a trend toward a higher hepatitis activity index and HCV load at 16 weeks after liver transplantation. 8 Interestingly, while both HHV-6 and CMV infection were common in this cohort, HHV-7 was not detected in the plasma of the patients. 8 This is similar to our finding of a lower rate of HHV-7 infection in the HCV-positive group vs. the HCV-negative group.…”

“…Some previous studies have suggested more rapid progression of HCV in liver transplant recipients coinfected with CMV or HHV-6. [7][8][9][10] Since viral interactions may be bidirectional, we evaluated whether HCV infection promoted herpesvirus replication using sensitive quantitative polymerase chain reaction assays. In this study of 177 liver transplant patients, there was no evidence for an immunomodulatory role for HCV with respect to herpesvirus reactivation.…”

“…Patients with CMV viremia had a higher mean total Knodell score at last follow-up and a higher incidence of cirrhosis. Razonable et al 8 investigated the effect of ␤-herpesviruses in 92 HCV-infected liver transplant recipients. CMV infection and disease, but not HHV-6 infection, were independently associated with allograft failure and mortality.…”

“…6 The interaction between herpesviruses and HCV has been proposed to be clinically important in HCV-infected liver transplant recipients. [7][8][9][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.…”