Efficacy of new direct acting antivirals in transplant recipients and patients with advanced disease.

The development of new direct acting antivirals constitutes a clinical revolution in the field of hepatitis C therapy and, most probably, in the history of Hepatology. Difficult-to-treat patients, such as cirrhotics or patients in the peri-transplant setting, will clearly benefit from these therapies, particularly from interferon-free all-oral combinations. However, despite the substantial improvement of the hepatitis C drug market, access to these therapies will likely be different around the world due to economic restrictions. This review aims to clarify the current stage of different antiviral strategies (with or without interferon) in these difficult populations by analysing specific efficacy and safety results in patients with cirrhosis, patients on the waiting list for liver transplantation and recipients with hepatitis C recurrence after liver transplantation. Hitherto, some important challenges still remain unanswered in these patients and will need to be assessed in clinical practice, such as the evaluation of safety and efficacy in advanced cirrhotic patients with portal hypertension, the impact (if any) of viral clearance on clinical outcomes in patients with decompensated liver disease, the role of ribavirin in all-oral combinations, the relevance of the development of multi-drug viral resistant strains and the drug-drug interaction profiles of these drugs, especially after liver transplantation.