title: Interferon-Free Hepatitis C Treatment before and after Liver Transplantation: The Role of HCV Drug Resistance.
abstract: Hepatitis C virus (HCV) infection is one of the leading causes of end-stage liver disease and the main indication for liver transplantation (LT) in most countries. All patients who undergo LT with detectable serum HCV RNA experience graft reinfection progressing to cirrhosis within five years in 20% to 30% of them. Obtaining a sustained virological response (SVR) greatly improves overall and graft survival. Until 2011, standard antiviral therapy using PEGylated interferon (PEG-IFN) and ribavirin (RBV) was the only effective therapy, with an SVR rate around 30% in this setting. For patients infected with genotype 1, first generation NS3/4A protease inhibitors (PIs), boceprevir (BOC) or telaprevir (TVR), associated with PEG-IFN and RBV for 48 weeks have increased the SVR rates to 60% in non-transplant patients. However, tolerability and drug-drug interactions with calcineurin inhibitors (CNI) are both limiting factors of their use in the liver transplant setting. Over recent years, the efficacy of antiviral C therapy has improved dramatically using new direct-acting antiviral (DAA) agents without PEG-IFN and/or RBV, leading to SVR rates over 90% in non-transplant patients. Results available for transplant patients showed a better efficacy and tolerability and less drug-drug interactions than with first wave PIs. However, some infrequent cases of viral resistance have been reported using PIs or NS5A inhibitors pre- or post-LT that can lead to difficulties in the management of these patients.
authors.affiliation: AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, 12-14 avenue Paul Vaillant-Couturier, Villejuif, F-94800, France. bruno.roche@aphp.fr.|Univ. Paris-Sud, UMR-S 1193, Université Paris-Saclay, 12-14 avenue Paul Vaillant-Couturier, Villejuif, F-94800, France. bruno.roche@aphp.fr.|Inserm, UMR-S 1193, Université Paris-Saclay, Villejuif F-94800, France. bruno.roche@aphp.fr.|Hepatinov, Villejuif, F-94800, France. bruno.roche@aphp.fr.
authors.forename: Bruno
authors.initials: B
authors.lastname: Roche
authors.affiliation: AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, 12-14 avenue Paul Vaillant-Couturier, Villejuif, F-94800, France. audrey.coilly@aphp.fr.|Univ. Paris-Sud, UMR-S 1193, Université Paris-Saclay, 12-14 avenue Paul Vaillant-Couturier, Villejuif, F-94800, France. audrey.coilly@aphp.fr.|Inserm, UMR-S 1193, Université Paris-Saclay, Villejuif F-94800, France. audrey.coilly@aphp.fr.|Hepatinov, Villejuif, F-94800, France. audrey.coilly@aphp.fr.
authors.forename: Audrey
authors.initials: A
authors.lastname: Coilly
authors.affiliation: Univ. Paris-Sud, UMR-S 1193, Université Paris-Saclay, 12-14 avenue Paul Vaillant-Couturier, Villejuif, F-94800, France.|Inserm, UMR-S 1193, Université Paris-Saclay, Villejuif F-94800, France.|Hepatinov, Villejuif, F-94800, France.|AP-HP Hôpital Paul-Brousse, Laboratoire de Virologie, Villejuif F-94800, France.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Roque-Afonso
authors.affiliation: AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, 12-14 avenue Paul Vaillant-Couturier, Villejuif, F-94800, France. didier.samuel@aphp.fr.|Univ. Paris-Sud, UMR-S 1193, Université Paris-Saclay, 12-14 avenue Paul Vaillant-Couturier, Villejuif, F-94800, France. didier.samuel@aphp.fr.|Inserm, UMR-S 1193, Université Paris-Saclay, Villejuif F-94800, France. didier.samuel@aphp.fr.|Hepatinov, Villejuif, F-94800, France. didier.samuel@aphp.fr.
authors.forename: Didier
authors.initials: D
authors.lastname: Samuel
mesh_terms: D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D064420:Drug-Related Side Effects and Adverse Reactions; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D016031:Liver Transplantation; D011480:Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D011480:Protease Inhibitors
keywords: antiviral therapy; boceprevir; daclatasvir; dasabuvir; direct-acting antiviral; hepatitis C; interferon; ledipasvir; liver transplantation; ombitasvir; paritaprevir; ribavirin; simeprevir; sofosbuvir; telaprevir