Management of Transplant Patients Infected with HCV

Abstract

Hepatitis C virus (HCV) infection is a leading cause of cirrhosis and hepatocellular carcinoma and one of the main indications for liver transplantation (LT) [1]. Historically, viral recurrence occurred in all patients with viral replication at the time of LT. Graft fibrosis progression rate was accelerated leading to cirrhosis in around 30% of untreated patients within 5 years. HCV graft infection was the cause of two-thirds of graft failure in these patients and was the most frequent cause of death [2, 3]. Viral eradication using antiviral therapy improves patient and graft survival [4–6]. Pegylated interferon (PEG-IFN)-ribavirin (RBV) and first-generation NS3/4 protease inhibitors (PI): boceprevir (BOC) or telaprevir (TVR) associated to PEG-IFN-RBV are no more used to treat HCV infection post-LT related to lower efficacy, poor tolerability, and drug–drug interactions (DDI) with immunosuppressive therapy [7–10]. Since 2013, the use of Sofosbuvir (SOF), a NS5B polymerase inhibitor, with RBV has led to improvements in tolerability and efficacy [11, 12]. Further improvement in SVR rates was observed using SOF in combination with a second direct-acting antiviral (DAA): Simeprevir (SIM), Ledipasvir (LDV), Daclatasvir (DCV), Elbasvir (EBR), and RBV, or the regimen of Ombitasvir, Paritaprevir/Ritonavir, Dasabuvir (3D), and RBV [13–28]. Limitations of these regimens are suboptimal efficacy in some subgroups of patients, none are pangenotypic, mostly contain RBV, and some have the potential for clinically significant DDIs. More recently, a new wave of pangenotypic, RBV-free, DAA regimens including SOF–Velpatasvir (VEL), Glecaprevir (GLE)–Pibrentasvir (PIB), and Voxaliprevir (VOX), were approved [29, 30]. These regimens maintain activity against most of the common resistance-associated substitutions (RAS) of HCV genotypes 1–6 that are known to confer resistance to previously approved antiviral therapies.