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. Infection of the engrafted liver is universal and accelerates progression to advanced liver disease, with 20-30% of patients having cirrhosis within 5 years of transplantation. Treatments of chronic HCV infection have improved dramatically, albeit with remaining challenges of failure and access, and therapeutic options to prevent graft infection during liver transplantation are emerging. Developments in directed use of new direct-acting antiviral agents (DAAs) to eliminate circulating HCV before or after transplantation in the past 5 years provide renewed hope for prevention and treatment of liver graft infection. Identification of the ideal regimen and use of DAAs reveals new ways to treat this specific population of patients. Complementing DAAs, viral entry inhibitors have been shown to prevent liver graft infection in animal models and delay graft infection in clinical trials, which shows their potential for use 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 used synergistically with DAAs to prevent or treat graft infection.
Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France; Université de Strasbourg, Strasbourg, France; Hepatology Research Group, Peninsula School of Medicine and Dentistry, University of Plymouth, Plymouth, UK.
Daniel J
DJ
Felmlee
AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, France; University Paris-Sud, UMR-S 1193, Villejuif, France; Inserm Unit 1193, Villejuif F-94800, France.
Audrey
A
Coilly
Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Raymond T
RT
Chung
AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, France; University Paris-Sud, UMR-S 1193, Villejuif, France; Inserm Unit 1193, Villejuif F-94800, France. Electronic address: didier.samuel@aphp.fr.
Didier
D
Samuel
Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France; Université de Strasbourg, Strasbourg, France; Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Institut Hospitalo-Universitaire, Pôle Hépato-digestif, Hôpitaux Universitaires de Strasbourg, Strasbourg, France. Electronic address: thomas.baumert@unistra.fr.
Thomas F
TF
Baumert
D000998:Antiviral Agents / Q000627:therapeutic use*; D018450:Disease Progression; D016174:Hepacivirus / Q000187:drug effects*; D006526:Hepatitis C / Q000188:drug therapy*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000209:etiology; D016031:Liver Transplantation; D014775:Virus Activation / Q000187:drug effects
D000998:Antiviral Agents