HCV treatment in liver transplantation: timing is the challenge.

Hepatitis C infection is one of the most common causes of chronic end-stage liver disease, with its sequelae decompensated liver cirrhosis and hepatocellular carcinoma. Both are currently the most important indications for liver transplantation [1]. Unfortunately, almost all patients with detectable HCV RNA at the time of transplantation will have recurrent hepatitis C in their graft [2]. Although spontaneous clearance can occur during primary infection [3], under immunosuppressive therapy this is rather rare [4]. Moreover, recurrent hepatitis C after liver transplantation follows a more rapid course, with the development of liver cirrhosis in approximately 20-40% of the patients within 5 years [5] and causing significant graft loss and even death. Until recently, the only possible treatment was (peg) interferon-based antiviral therapy. It has been clearly shown that obtaining sustained virological response even in the cirrhotic stage is associated with improved survival by a decrease in both all-cause and liver-related mortality [6]. In the setting of liver transplantation, the efficacy is significantly less due to poor tolerance and the occurrence of (severe) complications [7]. However, with the introduction of all oral interferon-free direct antiviral therapy this is past history and hepatitis C in the setting of liver transplantation can now be treated as in all other patients, obtaining similar results. In most countries where liver transplantation is being performed, hepatitis C after liver transplantation is being regarded an indication for antiviral therapy with high priority. Both the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases/Infectious Diseases Society of America advocate the use of direct antiviral agents (DAAs) after liver transplantation and have designed specific guidelines for the post-liver transplant setting [7–9]. With the approval of NS3/4a protease inhibitors (simeprevir, paritaprevir), NS5a polymerase inhibitors (daclatasvir, ombitasvir, ledipasvir), NS5b polymerase inhibitors (sofosbuvir, dasabuvir) and more to come, all patients after liver transplantation can now be treated, with almost similar high cure rates as in the non-liver transplant setting [10–13]. All DAA combinations are well tolerated, without any severe complication. In the setting of liver transplantation, important drug–drug interactions are to be expected, in particular because the