New perspectives for preventing hepatitis C virus liver graft infection

Hepatitis C virus (HCV) infection is a leading cause of end-stage liver disease that necessitates liver transplantation. The incidence of virus-induced cirrhosis and hepatocellular carcinoma continues to increase, making liver transplantation increasingly common(1–3). Infection of the engrafted liver is universal and increases progression to advanced liver disease, with 20–30% displaying cirrhosis within 5 years. While treatments of chronic HCV infection have improved dramatically, albeit with remaining challenges of failure and access, therapeutic options to prevent graft infection during liver transplantation are emerging. Recent developments in directed use of novel direct-acting antiviral (DAA) agents(4–6) to eliminate circulating HCV prior or following transplantation bring renewed hope for prevention and treatment of liver graft infection. Identifying the ideal regimen and use of DAAs reveals new paradigms of treatment for this special population(6–8). Complementing DAAs, entry inhibitors have been shown to prevent liver graft infection in animal models(9–13) and delay graft infection in clinical trials(14), providing a perspective to be used concomitant to transplantation. We review the challenges and pathology associated with HCV liver graft infection, highlight current and future strategies of DAA treatment timing, and discuss the potential role of entry inhibitors that might be employed synergistically with DAAs to inhibit graft infection.