Bidirectional Interaction between Cytomegalovirus and Hepatitis C Virus after Liver Transplantation: A Critical Review of the Clinical Evidence

Purpose: A bidirectional interaction between cytomegalovirus and hepatitis C is hypothesized to adversely affect the outcome of liver transplantation for chronic hepatitis C. This article reviews the clinical data on this hepatitis C virus-cytomegalovirus interaction. Methods: Review of (i) studies that assessed the impact of cytomegalovirus on hepatitis C virus viremia, recurrent hepatitis C, fibrosis, cirrhosis, graft failure, and mortality and (ii) studies that assessed the impact of hepatitis C virus on cytomegalovirus load, infection, and disease. Results: Eleven studies investigated the impact of cytomegalovirus on hepatitis C outcomes. Seven of these studies reported potential associations of cytomegalovirus with (i) time to recurrent hepatitis C and fibrosis, (ii) severity of recurrent hepatitis C and fibrosis, and/or (iii) incidence of allograft failure and mortality. In contrast, four studies failed to demonstrate these associations. On the issue of hepatitis C virus influencing cytomegalovirus outcomes, two studies reported a higher incidence of cytomegalovirus disease in liver recipients with severe recurrent hepatitis C, while two studies failed to show the association between hepatitis C virus positivity and cytomegalovirus load, infection, and disease after liver transplantation. Conclusion: This comprehensive review highlights the conflicting results of studies on the association between hepatitis C virus and cytomegalovirus after liver transplantation. The contrasting findings could be accounted for by several factors including variability in case definitions and endpoints, patient populations, clinical practices such as anti-cytomegalovirus prophylaxis and interferon therapy, among others. In our view, despite these conflicting results, the proven association between cytomegalovirus and overall transplant outcomes (and possibly hepatitis C virus pathogenicity) should warrant an aggressive cytomegalovirus prevention strategy in hepatitis C virus-infected liver transplant recipients. (Trends in Transplant. 2008;2:148-56) Corresponding author: Raymund R. Razonable, [email protected]