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

Abstract

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.

Cytomegalovirus infection after liver transplantation: Current concepts and challenges

“…In a study on 247 patients, HHV-6 seroconversion was an independent marker of CMV disease after liver transplantation. Likewise, HCVinfected liver transplant recipients also have a higher incidence of CMV disease [48] , although our data in the era of valganciclovir prophylaxis has refuted this observation [25] .…”

“…A well-described interaction between members of the beta-herpes group of viruses has been described, exemplified by the observation that reactivation of HHV-6 and HHV-7 is associated with an increased predisposition to CMV disease after liver transplantation [22][23][24] . In a similar manner, there is a significant association between CMV and hepatitis C virus [25][26][27][28][29][30] , manifested by an accelerated course of HCV recurrence in patients who develop CMV infection after liver transplantation. In our analysis of 92 HCVinfected liver transplant recipients, there was a four-fold higher risk of allograft failure and mortality in patients with CMV infection and disease [28,30] .…”

Hidden hazards of HCV transmission

“…Under the immunological point of view, these reports may be justiWed since on those clinical situations a immunosuppression established could be a factor predisposing to the viral agents reactivation such as, HBV, CMV (and other virus herpes), and HCV, as has been widely observed [50]. This Wnding, however, has only been possible when it is known the prior patient's serological status.…”

Current concepts on cytomegalovirus infection after liver transplantation

“…HHV6 has been associated with an increased predisposition to develop CMV disease after li ver transp lantation [22,23,25] . Likewise, HCVinfected liver transplant patients have a higher incidence of CMV disease [54] , al though the advent of valganciclovir prophylaxis has all owed mitigation of this phenomenon [26] .…”