Understanding the switchbacks: the impact of direct antivirals on the minimization of hepatitis C virus recurrence after transplantation.

1. Interferon (IFN) and ribavirin can be used in select patients before or after liver transplantation, and they can reduce the risk of recurrence or effect a cure in these settings. 2. Currently licensed direct-acting antiviral drugs are used with IFN and ribavirin, so the safety and tolerability of triple therapy will be worse than those of double therapy in pretransplant and posttransplant settings. 3. Drug-drug interactions [exemplified by the interactions of protease inhibitors (PIs) with tacrolimus and cyclosporine] and the need for dose modifications (exemplified by the need to modify ribavirin doses in patients with renal dysfunction) challenge the safe use of antiviral drugs after transplantation. 4. Experience with the use of human immunodeficiency virus PIs and emerging data about hepatitis C virus (HCV) PIs show that this class of drugs can be used with care after transplantation. 5. Attempts to prevent HCV graft infections through the use of HCV immunoglobulin immediately after transplantation have been largely unsuccessful. 6. The blockade of cell surface HCV receptors with antibodies or small molecules appears to limit HCV cell entry in vivo and in a mouse model, and this may suggest a novel approach to limiting HCV recurrence at the time of transplantation.