During 2014 and 2015, different interferon- (IFN-) free regimens will be approved for use in chronic hepatitis C (HCV). The liver-transplantation (LT) setting is the field of hepatology where these regimens will have the highest and fastest impact. Indeed, one study using direct-acting antivirals has already proven the concept that graft HCV infection can be prevented by treating patients awaiting LT. Safety and efficacy of several IFN-free regimens are currently being assessed in patients with hepatitis C recurrence after LT, with good preliminary results. Nevertheless, there are some issues that need to be addressed in the peri-LT setting and are reviewed in this article: (1) efficacy of IFN-free regimens in patients with advanced cirrhosis and portal hypertension, (2) pharmacokinetics of new antivirals in patients with several grades of hepatic or renal impairment, (3) impact of the selection of drug-resistant HCV strains in patients with decompensated cirrhosis or with severe hepatitis C recurrence after LT, and (4) drug-drug interactions.
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