Stanislas Pol1, Marc Bourliere2, Sandy Lucier3, Christophe Hezode4, Céline Dorival3, Dominique Larrey5, Jean-Pierre Bronowicki6, Victor D E Ledinghen7, Fabien Zoulim8, Albert Tran9, Sophie Metivier10, Jean-Pierre Zarski11, Didier Samuel12, Dominique Guyader13, Patrick Marcellin14, Anne Minello15, Laurent Alric16, Dominique Thabut17, Olivier Chazouilleres18, Ghassan Riachi19, Valérie Bourcier20, Philippe Mathurin21, Véronique Loustaud-Ratti22, Louis D'Alteroche23, Isabelle Fouchard-Hubert24, François Habersetzer25, Xavier Causse26, Claire Geist27, Isabelle Rosa28, Jérôme Gournay29, Eric Saillard30, Eric Billaud31, Ventzislava Petrov-Sanchez32, Alpha Diallo33, Hélène Fontaine34, Fabrice Carrat35. 1. Université Paris Descartes, AP-HP, Unité d'Hépatologie, Hôpital Cochin, INSERM U-1213 et USM20, Institut Pasteur, Paris, France. Electronic address: stanislas.pol@aphp.fr. 2. Department of Hepatology and Gastroenterology, Hôpital Saint Joseph, Marseille, France. 3. Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique (IPLESP UMRS 1136), F75012 Paris, France. 4. Department of Hepatology and Gastroenterology, Hôpital Henri Mondor, AP-HP, Université Paris-Est, INSERM U955, Créteil, France. 5. Liver unit-IRB-INSERM1040, Hôpital Saint Eloi, Montpellier, France. 6. Department of Hepatology and Gastroenterology, Centre Hospitalier Universitaire de Nancy, Université de Lorraine, INSERM U954, Vandoeuvre-lès-nancy, France. 7. Department of Hepatology and Gastroenterology, Hôpital Haut-Lévêque, Pessac, France; INSERM, U1053, Université Bordeaux Segalen, Bordeaux, France. 8. Department of Hepatology, Hospices Civils de Lyon, INSERM U1052, Université de Lyon, Lyon, France. 9. Digestive Centre, Centre Hospitalier Universitaire de Nice, INSERM U1065-8, Nice, France. 10. Department of Hepatology and Gastroenterology, CHU Purpan, Toulouse, France. 11. Department of Hepatology and Gastroenterology, Centre Hospitalo-Universitaire, INSERM U823, Grenoble, France. 12. Centre Hépato-Biliaire, Hôpital Paul Brousse, AP-HP, UMR-S785, Université Paris-Sud, INSERM U785, Villejuif, France. 13. Liver Disease Unit, CHU Rennes, Université de Rennes 1, INSERM U991, Rennes, France. 14. Department of Hepatology, Hôpital Beaujon, AP-HP, Université Paris-Diderot, INSERM CRB3, Clichy, France. 15. Department of Hepatology and Gastroenterology, Dijon University Hospital, Burgundy University, INSERM U866, France. 16. Internal Medicine-Digestive Department CHU Purpan, UMR152, IRD, Toulouse 3 University, France. 17. Department of Hepatology and Gastroenterology, Groupe Hospitalier Pitié-Salpétrière, AP-HP, Université Pierre et Marie Curie Paris 6, INSERM UMR-S938, Paris, France. 18. Department of Hepatology, Hôpital Saint-Antoine, AP-HP, Université Pierre et Marie Curie Paris 6, Paris, France. 19. Department of Hepatology and Gastroenterology, CHU Charles Nicolle, Rouen, France. 20. Department of Hepatology and Gastroenterology, Hôpital Jean Verdier, AP-HP, Université Paris 13, Bondy, France. 21. Department of Hepatology and Gastroenterology, Centre Hospitalier Régional et Universitaire Claude Huriez, Lille, France. 22. Department of Hepatology and Gastroenterology, CHU Limoges, U850 INSERM, Univ. Limoges, F-87000 Limoges, France. 23. Unit of Hepatology, Hépatogastroenterologie, CHU Trousseau, 37044 Tours, France. 24. Liver-Gastroenterology Department, CHU Angers, France. 25. Inserm CIC-1434, Inserm 1110 et Pôle Hépato-digestif des Hôpitaux Universitaires de Strasbourg, Strasbourg, France. 26. Department of Hepatology and Gastroenterology, CHR La Source, Orléans, France. 27. Department of Hepatology and Gastroenterology, Centre Hospitalier Régional, Metz, France. 28. Department of Hepatology and Gastroenterology, Centre Hospitalier Intercommunal, Créteil, France. 29. Department of Hepatology and Gastroenterology, Hôpital Hôtel-Dieu, Nantes, France. 30. Department of Gastroenterology, CHU de Pointe-à-Pitre, Guadeloupe, France. 31. Division of Infectious Diseases, University Hospital of Nantes, Nantes, France. 32. ANRS (France REcherche Nord&sud Sida-vih Hépatites), Unit for Basic and Clinical Research on Viral Hepatitis, Paris, France. 33. ANRS (France REcherche Nord&sud Sida-vih Hépatites), Clinical Trial Safety and Public Health, Paris, France. 34. Université Paris Descartes, AP-HP, Unité d'Hépatologie, Hôpital Cochin, INSERM U-1213 et USM20, Institut Pasteur, Paris, France. 35. Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique (IPLESP UMRS 1136), F75012 Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Antoine, Unité de Santé Publique, F-75012 Paris, France.
Abstract
BACKGROUND & AIMS: We report the first real-life results of the sofosbuvir+daclatasvir combination in hepatitis C virus (HCV) genotype 1 infected patients. METHODS: The France REcherche Nord&Sud Sida-hiv Hépatites (ANRS) CO22 HEPATHER "Therapeutic options for hepatitis B and C: A French cohort" is a multicentre observational cohort which aims to include 15,000 HCV- and 10,000 HBV-infected patients. We selected all participants (n=768) with a HCV genotype 1 who initiated sofosbuvir (400mg/day) and daclatasvir (60mg/day) before October 1st 2014, with or without ribavirin (1-1.2g/day) for a duration of 12weeks or 24weeks. The main endpoint criterion was sustained virological response at 12weeks (SVR12), defined by the absence of detectable HCV-RNA 12weeks after the last treatment intake. Missing SVR12 measurements were imputed using SVR24 measurements (n=45), otherwise considered as virological failure (n=18). RESULTS: A SVR12 was obtained in 729/768 (95%) patients, ranging from 92% (12-week sofosbuvir+daclatasvir) to 99% (24-week sofosbuvir+daclatasvir+ribavirin). The SVR12 rates did not significantly differ between the 24-week (550/574 (96%)) and the 12-week (179/194 (92%); p=0.0688) durations or between regimens with (165/169 (98%)) or without ribavirin (564/599 (94%); p=0.0850). The SVR12 rate was greater than 97% in non-cirrhotic patients irrespective of the treatment duration or the addition of ribavirin. Among cirrhotic patients, the SVR12 rate was higher with 24 than 12-week regimen (423/444 (95%) vs. 105/119 (88%); p=0.0054). CONCLUSION: The sofosbuvir+daclatasvir combination is associated with a high rate of SVR12 in patients infected by genotype 1, with an optimal duration of 12weeks in non-cirrhotic and 24weeks in cirrhotic patients. The number of patients receiving ribavirin was too low to adequately assess its impact. LAY SUMMARY: The sofosbuvir+daclatasvir combination of antiviral drugs is associated with a high rate (95%) of viral eradication in patients infected by HCV genotype 1. The best duration of a ribavirin-free sofosbuvir+daclatasvir combination seems to be 12weeks in non-cirrhotic patients and 24weeks for those with cirrhosis. Clinical trial number: NCT01953458. Copyright Â
BACKGROUND & AIMS: We report the first real-life results of the sofosbuvir+daclatasvir combination in hepatitis C virus (HCV) genotype 1 infected patients. METHODS: The France REcherche Nord&Sud Sida-hiv Hépatites (ANRS) CO22 HEPATHER "Therapeutic options for hepatitis B and C: A French cohort" is a multicentre observational cohort which aims to include 15,000 HCV- and 10,000 HBV-infectedpatients. We selected all participants (n=768) with a HCV genotype 1 who initiated sofosbuvir (400mg/day) and daclatasvir (60mg/day) before October 1st 2014, with or without ribavirin (1-1.2g/day) for a duration of 12weeks or 24weeks. The main endpoint criterion was sustained virological response at 12weeks (SVR12), defined by the absence of detectable HCV-RNA 12weeks after the last treatment intake. Missing SVR12 measurements were imputed using SVR24 measurements (n=45), otherwise considered as virological failure (n=18). RESULTS: A SVR12 was obtained in 729/768 (95%) patients, ranging from 92% (12-week sofosbuvir+daclatasvir) to 99% (24-week sofosbuvir+daclatasvir+ribavirin). The SVR12 rates did not significantly differ between the 24-week (550/574 (96%)) and the 12-week (179/194 (92%); p=0.0688) durations or between regimens with (165/169 (98%)) or without ribavirin (564/599 (94%); p=0.0850). The SVR12 rate was greater than 97% in non-cirrhotic patients irrespective of the treatment duration or the addition of ribavirin. Among cirrhotic patients, the SVR12 rate was higher with 24 than 12-week regimen (423/444 (95%) vs. 105/119 (88%); p=0.0054). CONCLUSION: The sofosbuvir+daclatasvir combination is associated with a high rate of SVR12 in patients infected by genotype 1, with an optimal duration of 12weeks in non-cirrhotic and 24weeks in cirrhotic patients. The number of patients receiving ribavirin was too low to adequately assess its impact. LAY SUMMARY: The sofosbuvir+daclatasvir combination of antiviral drugs is associated with a high rate (95%) of viral eradication in patients infected by HCV genotype 1. The best duration of a ribavirin-free sofosbuvir+daclatasvir combination seems to be 12weeks in non-cirrhotic patients and 24weeks for those with cirrhosis. Clinical trial number: NCT01953458. Copyright Â
Authors: Rodolfo Castro; Louise Crathorne; Hugo Perazzo; Julio Silva; Chris Cooper; Jo Varley-Campbell; Daniel Savignon Marinho; Marcela Haasova; Valdilea G Veloso; Rob Anderson; Chris Hyde Journal: BMC Med Res Methodol Date: 2018-06-13 Impact factor: 4.615