Christophe Hézode1, Helene Fontaine2, Celine Dorival3, Fabien Zoulim4, Dominique Larrey5, Valerie Canva6, Victor De Ledinghen7, Thierry Poynard8, Didier Samuel9, Marc Bourliere10, Laurent Alric11, Jean-Jacques Raabe12, Jean-Pierre Zarski13, Patrick Marcellin14, Ghassan Riachi15, Pierre-Henri Bernard16, Veronique Loustaud-Ratti17, Olivier Chazouilleres18, Armand Abergel19, Dominique Guyader20, Sophie Metivier21, Albert Tran22, Vincent Di Martino23, Xavier Causse24, Thong Dao25, Damien Lucidarme26, Isabelle Portal27, Patrice Cacoub28, Jerome Gournay29, Veronique Grando-Lemaire30, Patrick Hillon31, Pierre Attali32, Thierry Fontanges33, Isabelle Rosa34, Ventzislava Petrov-Sanchez35, Yoann Barthe3, Jean-Michel Pawlotsky36, Stanislas Pol2, Fabrice Carrat37, Jean-Pierre Bronowicki38. 1. Department of Hepatology and Gastroenterology, Hôpital Henri Mondor, AP-HP, Université Paris-Est, INSERM U955, Créteil, France. 2. Department of Hepatology, Hôpital Cochin, AP-HP, Université Paris-René Descartes, INSERM U1016, Paris, France. 3. INSERM UMR-S 1136, Université Pierre et Marie Curie Paris 6, Paris, France. 4. Department of Hepatology, Hospices Civils de Lyon, INSERM U1052, Université de Lyon, Lyon, France. 5. Liver Unit-IRB-INSERM1040, Hôpital Saint Eloi, Montpellier, France. 6. Department of Hepatology and Gastroenterology, Centre Hospitalier Régional et Universitaire Claude Huriez, Lille, France. 7. Department of Hepatology and Gastroenterology, Hôpital Haut-Lévêque, Pessac, INSERM U1053, Université Bordeaux Segalen, Bordeaux, France. 8. Department of Hepatology and Gastroenterology, Groupe Hospitalier Pitié-Salpétrière, AP-HP, Université Pierre et Marie Curie Paris 6, INSERM UMR-S938, Paris, France. 9. Centre Hépato-Biliaire, Hôpital Paul Brousse, AP-HP, UMR-S785, Université Paris-Sud, INSERM U785, Villejuif, France. 10. Department of Hepatology and Gastroenterology, Hôpital Saint Joseph, Marseille, France. 11. Department of Internal Medicine and Digestive Diseases, UMR-152, Toulouse III University, Toulouse, France. 12. Department of Hepatology and Gastroenterology, Centre Hospitalier Régional, Metz, France. 13. Department of Hepatology and Gastroenterology, Centre Hospitalo-Universitaire, INSERM U823, Grenoble, France. 14. Department of Hepatology, Hôpital Beaujon, AP-HP, Université Paris-Diderot, INSERM CRB3, Clichy, France. 15. Department of Hepatology and Gastroenterology, CHU Charles Nicolle, Rouen, France. 16. Service d'Hépatologie et Gastroentérologie, Hôpital Saint-André, Bordeaux, INSERM U1053, Université Bordeaux Segalen, Bordeaux, France. 17. Department of Hepatology and Gastroenterology, CHU Dupuytren, Université de Limoges, UMR INSERM U1092, Limoges, France. 18. Department of Hepatology, Hôpital Saint-Antoine, AP-HP, Paris, France. 19. Department of Hepatology and Gastroenterology, CHU Estaing, Université d'Auvergne, UMR 6284, Clermont-Ferrand, France. 20. Service des Maladies du Foie, CHU Rennes, Université de Rennes 1, INSERM U991, Rennes, France. 21. Department of Hepatology and Gastroenterology, CHU Purpan, Toulouse, France. 22. Digestive Center, Centre Hospitalier Universitaire de Nice, INSERM U1065-8, Nice, France. 23. Service d'Hépatologie, CHU Jean Minjoz, Université de Franche Comté, Besançon, France. 24. Department of Hepatology and Gastroenterology and Digestive Oncology, CHR La Source, Orléans, France. 25. Department of Hepatology and Gastroenterology, CHU, INSERM U1075, Caen, France. 26. Department of Hepatology and Gastroenterology, Groupe Hospitalier de l'Institut Catholique Lillois, Faculté Libre de Médecine, Lille, France. 27. Department of Hepatology and Gastroenterology, Hôpital de la Conception, Marseille, France. 28. Department of Internal Medicine, Groupe Hospitalier Pitié-Salpêtrière, AP-HP, Université Pierre et Marie Curie Paris 6, INSERM, UMR-S959, CNRS, UMR 7211, Paris, France. 29. Department of Hepatology and Gastroenterology, Hôpital Hôtel-Dieu, Nantes, France. 30. Department of Hepatology and Gastroenterology, Hôpital Jean Verdier, AP-HP, Université Paris 13, Bondy, France. 31. Department of Hepatology and Gastroenterology, CHU de Dijon, Université de Bourgogne, Dijon, France. 32. Department of Hepatology and Gastroenterology, Hôpital de Bicêtre, AP-HP, Le Kremlin-Bicêtre, France. 33. Department of Hepatology and Gastroenterology, Hôpital P Oudot, Bourgoin-Jallieu, France. 34. Department of Hepatology and Gastroenterology, Centre Hospitalier Intercommunal, Créteil, France. 35. Unit for Basic and Clinical Research on Viral Hepatitis, French National Agency for Research on AIDS and Viral Hepatitis, Paris, France. 36. National Reference Center for Viral Hepatitis B, C and Delta, Department of Virology, Hôpital Henri Mondor, AP-HP, Université Paris-Est, INSERM U955, Créteil, France. 37. INSERM UMR-S 1136, Université Pierre et Marie Curie Paris 6, Paris, France; Department of Public Health, Hôpital Saint-Antoine, AP-HP, Paris, France. 38. Department of Hepatology and Gastroenterology, Centre Hospitalier Universitaire de Nancy, Université de Lorraine, INSERM U954, Vandoeuvre-les-Nancy, France. Electronic address: jp.bronowicki@chu-nancy.fr.
Abstract
BACKGROUND & AIMS: We investigated the effectiveness of the protease inhibitors peginterferon and ribavirin in treatment-experienced patients with hepatitis C virus (HCV) genotype 1 infection and cirrhosis. METHODS: In the Compassionate Use of Protease Inhibitors in Viral C Cirrhosis study, 511 patients with HCV genotype 1 infection and compensated cirrhosis who did not respond to a prior course of peginterferon and ribavirin (44.3% relapsers or patients with viral breakthrough, 44.8% partial responders, and 8.0% null responders) were given either telaprevir (n = 299) or boceprevir (n = 212) for 48 weeks. We assessed percentages of patients with sustained viral responses 12 weeks after therapy and safety. This observational study did not allow for direct comparison of the 2 regimens. RESULTS: Among patients given telaprevir, 74.2% of relapsers, 40.0% of partial responders, and 19.4% of null responders achieved SVR12. Among those given boceprevir, 53.9% of relapsers, 38.3% of partial responders, and none of the null responders achieved SVR12. In multivariate analysis, factors associated with SVR12 included prior response to treatment response, no lead-in phase, HCV subtype 1b (vs 1a), and baseline platelet count greater than 100,000/mm(3). Severe adverse events occurred in 49.9% of cases, including liver decompensation, severe infections in 10.4%, and death in 2.2%. In multivariate analysis, baseline serum albumin level less than 35 g/L and baseline platelet counts of 100,000/mm(3) or less predicted severe side effects or death. CONCLUSIONS: Relatively high percentages of real-life, treatment-experienced patients with HCV genotype 1 infection and cirrhosis respond to the combination of peginterferon and ribavirin with telaprevir or boceprevir. However, side effects are frequent and often severe. Baseline levels of albumin and platelet counts can be used to guide treatment decisions. ClinicalTrials.gov number: NCT01514890.
BACKGROUND & AIMS: We investigated the effectiveness of the protease inhibitors peginterferon and ribavirin in treatment-experienced patients with hepatitis C virus (HCV) genotype 1 infection and cirrhosis. METHODS: In the Compassionate Use of Protease Inhibitors in Viral C Cirrhosis study, 511 patients with HCV genotype 1 infection and compensated cirrhosis who did not respond to a prior course of peginterferon and ribavirin (44.3% relapsers or patients with viral breakthrough, 44.8% partial responders, and 8.0% null responders) were given either telaprevir (n = 299) or boceprevir (n = 212) for 48 weeks. We assessed percentages of patients with sustained viral responses 12 weeks after therapy and safety. This observational study did not allow for direct comparison of the 2 regimens. RESULTS: Among patients given telaprevir, 74.2% of relapsers, 40.0% of partial responders, and 19.4% of null responders achieved SVR12. Among those given boceprevir, 53.9% of relapsers, 38.3% of partial responders, and none of the null responders achieved SVR12. In multivariate analysis, factors associated with SVR12 included prior response to treatment response, no lead-in phase, HCV subtype 1b (vs 1a), and baseline platelet count greater than 100,000/mm(3). Severe adverse events occurred in 49.9% of cases, including liver decompensation, severe infections in 10.4%, and death in 2.2%. In multivariate analysis, baseline serum albumin level less than 35 g/L and baseline platelet counts of 100,000/mm(3) or less predicted severe side effects or death. CONCLUSIONS: Relatively high percentages of real-life, treatment-experienced patients with HCV genotype 1 infection and cirrhosis respond to the combination of peginterferon and ribavirin with telaprevir or boceprevir. However, side effects are frequent and often severe. Baseline levels of albumin and platelet counts can be used to guide treatment decisions. ClinicalTrials.gov number: NCT01514890.
Authors: Alex I Aspinall; Abdel A Shaheen; Golasa S Kochaksaraei; Breean Haslam; Samuel S Lee; Gisela Macphail; Jeff Kapler; Oscar E Larios; Kelly W Burak; Mark G Swain; Meredith A Borman; Carla S Coffin Journal: CMAJ Open Date: 2018-01-05
Authors: Javier Salmerón; Carmen Vinaixa; Rubén Berenguer; Juan Manuel Pascasio; Juan José Sánchez Ruano; Miguel Ángel Serra; Ana Gila; Moisés Diago; Manuel Romero-Gómez; José María Navarro; Milagros Testillano; Conrado Fernández; Dolores Espinosa; Isabel Carmona; José Antonio Pons; Francisco Jorquera; Francisco Javier Rodriguez; Ramón Pérez; José Luis Montero; Rafael Granados; Miguel Fernández; Ana Belén Martín; Paloma Muñoz de Rueda; Rosa Quiles Journal: World J Gastroenterol Date: 2015-08-14 Impact factor: 5.742
Authors: Antonio Ascione; Luigi Elio Adinolfi; Pietro Amoroso; Angelo Andriulli; Orlando Armignacco; Tiziana Ascione; Sergio Babudieri; Giorgio Barbarini; Michele Brogna; Francesco Cesario; Vincenzo Citro; Ernesto Claar; Raffaele Cozzolongo; Giuseppe D'Adamo; Emilio D'Amico; Pellegrino Dattolo; Massimo De Luca; Vincenzo De Maria; Massimo De Siena; Giuseppe De Vita; Antonio Di Giacomo; Rosanna De Marco; Giorgio De Stefano; Giulio De Stefano; Sebastiano Di Salvo; Raffaele Di Sarno; Nunzia Farella; Laura Felicioni; Basilio Fimiani; Luca Fontanella; Giuseppe Foti; Caterina Furlan; Francesca Giancotti; Giancarlo Giolitto; Tiziana Gravina; Barbara Guerrera; Roberto Gulminetti; Angelo Iacobellis; Michele Imparato; Angelo Iodice; Vincenzo Iovinella; Antonio Izzi; Alfonso Liberti; Pietro Leo; Gennaro Lettieri; Ileana Luppino; Aldo Marrone; Ettore Mazzoni; Vincenzo Messina; Roberto Monarca; Vincenzo Narciso; Lorenzo Nosotti; Adriano Maria Pellicelli; Alessandro Perrella; Guido Piai; Antonio Picardi; Paola Pierri; Grazia Pietromatera; Francesco Resta; Luca Rinaldi; Mario Romano; Angelo Rossini; Maurizio Russello; Grazia Russo; Rodolfo Sacco; Vincenzo Sangiovanni; Antonio Schiano; Antonio Sciambra; Gaetano Scifo; Filomena Simeone; Annarita Sullo; Pierluigi Tarquini; Paolo Tundo; Alfredo Vallone Journal: World J Hepatol Date: 2016-08-08