The Activation of Cytomegalovirus and Human Herpes Virus 6 After Liver Transplantation

Abstract

Background: Cytomegalovirus (CMV) and Human Herpes Virus-6 (HHV-6) activation after liver transplantation have been associated with increased graft rejection and adverse outcomes. This study aimed at investigating the development and timing of CMV infection after liver transplantation and its relation to post-transplantation HHV-6 activation. Methods: Patients undergoing liver transplantation were enrolled, regardless of their age, place of residence, or their liver failure etiology. Blood samples were collected at baseline and every week for a period of 12 weeks and were tested for anti-CMV IgG and anti-HHV-6 IgG, CMV pp65 antigenemia, as well as CMV and HHV-6 DNA using the Polymerase Chain Reaction (PCR) method. Results: Among 46 liver transplant recipients, 17 (36.9%) developed CMV infection within 3 months after transplantation. Before transplantation, 42 (91.3%) and 41 (89.1%) recipients were seropositive for CMV and HHV-6, respectively. Fifty percent of patients were positive for CMV antigenemia, among which 73.9% became symptomatic for CMV infection. Half of the patients had positive test results for CMV PCR with a significant relationship between the CMV viral load and the development of symptomatic CMV infection (P = 0.001). Twenty-five (54.3%) patients had positive test results for HHV-6 PCR with a significant relationship between HHV-6 positivity and the development of clinical presentation (P = 0.002). The average post-transplantation time to HHV-6 and CMV activation was 19.4 ± 86.5 and 28.4 ± 60.5 days, respectively, with a linear relationship in the regression analysis. Conclusions: The HHV-6 infection, either as primary infection or reactivation, leads to an increased risk of CMV infection and symptomatic disease after liver transplantation. Activation of HHV-6 precedes the CMV activation in time.