Audrey Coilly1, Claire Fougerou-Leurent2, Victor de Ledinghen3, Pauline Houssel-Debry4, Christophe Duvoux5, Vincent Di Martino6, Sylvie Radenne7, Nassim Kamar8, Louis D'Alteroche9, Vincent Leroy10, Valérie Canva11, Pascal Lebray12, Christophe Moreno13, Jérôme Dumortier14, Christine Silvain15, Camille Besch16, Philippe Perre17, Danielle Botta-Fridlund18, Rodolphe Anty19, Claire Francoz20, Armando Abergel21, Maryline Debette-Gratien22, Filomena Conti12, François Habersetzer23, Alexandra Rohel24, Emilie Rossignol2, Hélène Danjou2, Anne-Marie Roque-Afonso25, Didier Samuel26, Jean-Charles Duclos-Vallée26, Georges-Philippe Pageaux27. 1. AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif F-94800, France; Université Paris Sud, Université Paris Sud-Saclay, UMR-S 1193, Villejuif F-94800, France; INSERM, Unité 1193, Villejuif F-94800, France; DHU Hepatinov, Villejuif F-94800, France. Electronic address: audrey.coilly@aphp.fr. 2. Hôpital Universitaire de Pontchaillou, Service de Pharmacologie, Rennes, France; INSERM, CIC 1414 Clinical Investigation Centre, Rennes, France. 3. Service d'Hépato-Gastroentérologie, Hôpital Haut-Lévêque, CHU Bordeaux, & INSERM U1053, Bordeaux, France. 4. Hôpital Universitaire de Pontchaillou, Service d'Hépatologie et Transplantation Hépatique, Rennes, France. 5. Service d'Hépatologie, Hôpital Henri-Mondor, AP-HP, 94000 Créteil, France. 6. Service d'Hépatologie, CHRU Jean Minjoz et Université de Franche-Comté, Besançon, France. 7. Service d'Hépatologie, HCL, Hôpital de la Croix-Rousse, 69205 Lyon, France. 8. Département de Néphrologie et Transplantation d'Organes, CHU Rangueil, INSERM U1043, IFR-BMT, Université Paul Sabatier, Toulouse, France. 9. Service Hépato-gastro-entérologie, CHU Tours, France. 10. Clinique Universitaire d'Hépato-Gastroentérologie, Pôle Digidune, CHU de Grenoble, France. 11. CHRU de Lille, Service d'Hépatologie, Hôpital Huriez, CHRU Lille, 59037 Lille, France. 12. Service d'Hépatologie et de Transplantation Hépatique, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Paris, France. 13. Département de Gastroenterologie, d'Hépatopancréatologie et Cancérologie Digestive, CUB Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium. 14. Unité de Transplantation Hépatique, Fédération des Spécialités Digestives, Hôpital Edouard Herriot, Hospices Civils de Lyon et Université Claude Bernard Lyon 1, Lyon, France. 15. Service Hépato-gastro-entérologie, CHU Poitiers, France. 16. Centre de Chirurgie Digestive et Transplantation Hépatique, Université de Strasbourg, France. 17. Service de MPU Infectiologie CHD Vendée, 85925 La Roche sur Yon, France. 18. CHU Timone, Service d'Hépato-gastroentérologie, Marseille F-13005, France. 19. Hôpital universitaire de Nice, Service d'Hépato-gastroentérologie, INSERM, U1065, Equipe 8, Université de Nice-Sophia-Antipolis, Faculté de Médecine, Nice F-06107, Cedex 2, France. 20. Service d'Hépatologie, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, France. 21. Service d'Hépato-gastroentérologie, CHU Estaing Clermont-Ferrand, Clermont-Ferrand, France. 22. Service d'Hépato-gastroentérologie, CHU Limoges, Limoges, France. 23. Hôpitaux Universitaires de Strasbourg, Inserm U 1110, LabEx HepSYS, Université de Strasbourg, Strasbourg, France. 24. Unité de recherché Clinique et Fondamentale sur les Hépatites Virales, Agence Nationale de Recherche sur le Sida et les Hépatites Virales, Paris, France. 25. AP-HP Hôpital Paul-Brousse, Service de Virologie, Villejuif F-94800, France; Université Paris Sud, Université Paris Sud-Saclay, UMR-S 1193, Villejuif F-94800, France; INSERM, Unité 1193, Villejuif F-94800, France; DHU Hepatinov, Villejuif F-94800, France. 26. AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif F-94800, France; Université Paris Sud, Université Paris Sud-Saclay, UMR-S 1193, Villejuif F-94800, France; INSERM, Unité 1193, Villejuif F-94800, France; DHU Hepatinov, Villejuif F-94800, France. 27. Département d'Hépato-gastroentérologie et de Transplantation Hépatique, CHU Saint-Eloi, Université de Montpellier, Montpellier F-34295, France.
Abstract
BACKGROUND & AIMS: HCV recurrence remains a major issue in the liver transplant field, as it has a negative impact on both graft and patient survival. The purpose of this study was to investigate the efficacy and safety of treating HCV recurrence with sofosbuvir (SOF) and daclatasvir (DCV) combination therapy. METHODS: From October 2013 to March 2015, 559 liver recipients were enrolled in the prospective multicentre France REcherche Nord&Sud Sida-hiv Hépatites (ANRS) Compassionate use of Protease Inhibitors in viral C Liver Transplantation cohort. We selected 137 patients with an HCV recurrence receiving SOF and DCV, whatever the genotype or fibrosis stage. The use of ribavirin and the duration of therapy were at the investigator's discretion. The primary efficacy end point was a sustained virological response (SVR) 12weeks after the end of treatment. RESULTS: The SVR rate 12weeks after completing treatment was 96% under the intention-to treat analysis and 99% when excluding non-virological failures. Only two patients experienced a virological failure. The serious adverse event (SAE) rate reached 17.5%. Four patients (3%) stopped their treatment prematurely because of SAEs. Anaemia was the most common AE, with significantly more cases in the ribavirin group (56% vs. 18%; p<0.0001). A slight but significant reduction in creatinine clearance was reported. No clinically relevant drug-drug interactions were noted, but 52% of patients required a change to the dosage of immunosuppressive drugs. CONCLUSIONS: Treatment with SOF plus DCV was associated with a high SVR12 and low rates of serious adverse events among liver recipients with HCV recurrence. LAY SUMMARY: The recurrence of hepatitis C used to be the first cause of graft failure in infected liver transplanted recipients. Our study demonstrates the great efficacy of one combination of new all-oral direct-acting antiviral, sofosbuvir and daclatasvir, to treat the recurrence of hepatitis C on the graft. Ninety-six per cent of recipients were cured. The safety profile of this combination seemed to be good, especially no relevant drug-drug interaction with immunosuppressive drugs.
BACKGROUND & AIMS: HCV recurrence remains a major issue in the liver transplant field, as it has a negative impact on both graft and patient survival. The purpose of this study was to investigate the efficacy and safety of treating HCV recurrence with sofosbuvir (SOF) and daclatasvir (DCV) combination therapy. METHODS: From October 2013 to March 2015, 559 liver recipients were enrolled in the prospective multicentre France REcherche Nord&Sud Sida-hiv Hépatites (ANRS) Compassionate use of Protease Inhibitors in viral C Liver Transplantation cohort. We selected 137 patients with an HCV recurrence receiving SOF and DCV, whatever the genotype or fibrosis stage. The use of ribavirin and the duration of therapy were at the investigator's discretion. The primary efficacy end point was a sustained virological response (SVR) 12weeks after the end of treatment. RESULTS: The SVR rate 12weeks after completing treatment was 96% under the intention-to treat analysis and 99% when excluding non-virological failures. Only two patients experienced a virological failure. The serious adverse event (SAE) rate reached 17.5%. Four patients (3%) stopped their treatment prematurely because of SAEs. Anaemia was the most common AE, with significantly more cases in the ribavirin group (56% vs. 18%; p<0.0001). A slight but significant reduction in creatinine clearance was reported. No clinically relevant drug-drug interactions were noted, but 52% of patients required a change to the dosage of immunosuppressive drugs. CONCLUSIONS: Treatment with SOF plus DCV was associated with a high SVR12 and low rates of serious adverse events among liver recipients with HCV recurrence. LAY SUMMARY: The recurrence of hepatitis C used to be the first cause of graft failure in infected liver transplanted recipients. Our study demonstrates the great efficacy of one combination of new all-oral direct-acting antiviral, sofosbuvir and daclatasvir, to treat the recurrence of hepatitis C on the graft. Ninety-six per cent of recipients were cured. The safety profile of this combination seemed to be good, especially no relevant drug-drug interaction with immunosuppressive drugs.
Authors: Jim Young; Nina Weis; Harald Hofer; William Irving; Ola Weiland; Emiliano Giostra; Juan Manuel Pascasio; Lluis Castells; Martin Prieto; Roelien Postema; Cinira Lefevre; David Evans; Heiner C Bucher; Jose Luis Calleja Journal: BMC Infect Dis Date: 2017-01-07 Impact factor: 3.090
Authors: Sebastian Bernuth; Daniel Grimm; Johanna Vollmar; Felix Darstein; Jens Mittler; Michael Heise; Maria Hoppe-Lotichius; Peter R Galle; Hauke Lang; Tim Zimmermann Journal: Drug Des Devel Ther Date: 2017-07-12 Impact factor: 4.162
Authors: Sammy Saab; Justin Rheem; Melissa A Jimenez; Tiffany M Fong; Michelle H Mai; Caterina A Kachadoorian; Negin L Esmailzadeh; Sherona N Bau; Susan Kang; Samantha D Ramirez; Jonathan Grotts; Gina Choi; Francisco A Durazo; Mohammed M El-Kabany; Steven-Huy B Han; Ronald W Busuttil Journal: J Clin Transl Hepatol Date: 2017-05-14
Authors: Julia M Grottenthaler; Christoph R Werner; Martina Steurer; Ulrich Spengler; Thomas Berg; Cornelius Engelmann; Heiner Wedemeyer; Thomas von Hahn; Wolfgang Stremmel; Anita Pathil; Ulrich Seybold; Eckart Schott; Usha Blessin; Christoph Sarrazin; Martin-Walter Welker; Ellen Harrer; Stefan Scholten; Clemens Hinterleitner; Ulrich M Lauer; Nisar P Malek; Christoph P Berg Journal: PLoS One Date: 2018-06-06 Impact factor: 3.240
Authors: Paul Kwo; Michael W Fried; K Rajender Reddy; Consuelo Soldevila-Pico; Saro Khemichian; Jama Darling; Phillippe J Zamor; Andrew A Napoli; Beatrice Anduze-Faris; Robert S Brown Journal: Hepatol Commun Date: 2018-02-27