Jordi Llaneras1, Mar Riveiro-Barciela2, Sabela Lens3, Moisés Diago4, Alba Cachero5, Javier García-Samaniego6, Isabel Conde7, Ana Arencibia8, Juan Arenas9, Francisco Gea10, Xavier Torras11, José Luis Calleja12, José Antonio Carrión13, Inmaculada Fernández14, Rosa María Morillas15, José Miguel Rosales16, Isabel Carmona17, Conrado Fernández-Rodríguez18, Manuel Hernández-Guerra19, Susana Llerena20, Vanesa Bernal21, Juan Turnes22, Jesús M González-Santiago23, Silvia Montoliu24, Blanca Figueruela25, Ester Badia26, Manuel Delgado27, Miguel Fernández-Bermejo28, Mercedes Iñarrairaegui29, Juan Manuel Pascasio30, Rafael Esteban2, Zoe Mariño3, Maria Buti31. 1. Hospital Universitari Vall d'Hebron, Department of Medicine of the UAB (Universitat Autònoma de Barcelona), Spain. 2. Hospital Universitari Vall d'Hebron, Department of Medicine of the UAB (Universitat Autònoma de Barcelona), Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain. 3. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain; Hospital Clínic, Barcelona, IDIBAPS, Universidad de Barcelona, Spain. 4. Hospital General Universitario de Valencia, Valencia, Spain. 5. Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Spain. 6. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain; Hospital Universitario La Paz, IdiPAZ, Madrid, Spain. 7. Hospital Universitario y Politécnico La Fe de Valencia, Valencia, Spain. 8. Hospital Universitario Nuestra Señora de La Candelaria, Santa Cruz de Tenerife, Spain. 9. Hospital Universitario Donostia, Donostia, Spain. 10. Hospital Ramón y Cajal, Madrid, Spain. 11. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain; Hospital Universitari de Santa Creu i Sant Pau, Barcelona, Spain. 12. Hospital Universitario Puerta del Hierro, Madrid, Spain. 13. Liver Section, Gastroenterology Department, Hospital del Mar, IMIM (Hospital del Mar Medical Research Institute), UAB (Universitat Autònoma de Barcelona), Barcelona, Spain. 14. Hospital 12 de Octubre, Madrid, Spain. 15. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain; Hospital Universitari Germans Trias i Pujol, Badalona, Spain. 16. Hospital Costa del Sol, Málaga, Spain. 17. Hospital Virgen de la Macarena, Seville, Spain. 18. Hospital Universitario Fundación Alcorcon, Madrid, Spain. 19. Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain. 20. Hospital Universitario Marqués de Valdecilla, Santander, Spain. 21. Hospital Miguel Servet, Zaragoza, Spain. 22. Complejo Hospitalario Universitario de Pontevedra, Pontevedra, Spain. 23. Complejo Asistencial Universitario de Salamanca, Salamanca, Spain. 24. Hospital Joan XXIII, Tarragona, Spain. 25. Hospital Virgen de Valme, Seville, Spain. 26. Hospital Universitario de Burgos, Burgos, Spain. 27. Hospital Universitario A Coruña, la Coruña, Spain. 28. Hospital Universitario San Pedro de Alcántara, Cáceres, Spain. 29. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain; Clínica Universidad de Navarra, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Navarra, Spain. 30. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain; Hospital Universitario Virgen del Rocío, Seville, Spain. 31. Hospital Universitari Vall d'Hebron, Department of Medicine of the UAB (Universitat Autònoma de Barcelona), Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain. Electronic address: mbuti@vhebron.net.
Abstract
BACKGROUND & AIMS: Around 5% of patients with chronic hepatitis C virus (HCV) infection treated with direct-acting antiviral (DAA) agents do not achieve sustained virological response (SVR). The currently approved retreatment regimen for prior DAA failure is a combination of sofosbuvir, velpatasvir, and voxilaprevir (SOF/VEL/VOX), although there is little data on its use in clinical practice. The aim of this study was to analyse the effectiveness and safety of SOF/VEL/VOX in the real-world setting. METHODS: This was a prospective multicentre study assessing the efficacy of retreatment with SOF/VEL/VOX in patients who had experienced a prior DAA treatment failure. The primary endpoint was SVR 12 weeks after the completion of treatment (SVR12). Data on safety and tolerability were also recorded. RESULTS: A total of 137 patients were included: 75% men, 35% with liver cirrhosis. Most were infected with HCV genotype (GT) 1 or 3. The most common prior DAA combinations were sofosbuvir plus an NS5A inhibitor or ombitasvir/paritaprevir/r+dasabuvir. A total of 136 (99%) patients achieved undetectable HCV RNA at the end of treatment. Overall SVR12 was 95% in the 135 patients reaching this point. SVR12 was lower in patients with cirrhosis (89%, p = 0.05) and those with GT3 infection (80%, p <0.001). Patients with GT3 infection and cirrhosis had the lowest SVR12 rate (69%). Of the patients who did not achieve SVR12, 1 was reinfected and 7 experienced treatment failure (6 GT3, 1 GT1a). The presence of resistance-associated substitutions did not impact SVR12. Adverse effects were mild and non-specific. CONCLUSION: Real-world data show that SOF/VEL/VOX is an effective, safe rescue therapy for patients with prior DAA treatment failure despite the presence of resistance-associated substitutions. However, patients with liver cirrhosis infected by GT3 remain the most-difficult-to-treat group. LAY SUMMARY: Treatment with sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) for 12 weeks is the current recommendation for the 5% of patients infected with HCV who do not achieve eradication of the virus under treatment with direct-acting antivirals. In a Spanish cohort of 137 patients who failed a previous combination of direct-acting antivirals, a cure rate of 95% was achieved with SOF/VEL/VOX. Genotypic characteristics of the virus (genotype 3) and the presence of cirrhosis were factors that decreased the rate of cure. Treatment with SOF/VEL/VOX is an effective and safe rescue therapy due to its high efficacy and very good safety profile.
BACKGROUND & AIMS: Around 5% of patients with chronic hepatitis C virus (HCV) infection treated with direct-acting antiviral (DAA) agents do not achieve sustained virological response (SVR). The currently approved retreatment regimen for prior DAA failure is a combination of sofosbuvir, velpatasvir, and voxilaprevir (SOF/VEL/VOX), although there is little data on its use in clinical practice. The aim of this study was to analyse the effectiveness and safety of SOF/VEL/VOX in the real-world setting. METHODS: This was a prospective multicentre study assessing the efficacy of retreatment with SOF/VEL/VOX in patients who had experienced a prior DAA treatment failure. The primary endpoint was SVR 12 weeks after the completion of treatment (SVR12). Data on safety and tolerability were also recorded. RESULTS: A total of 137 patients were included: 75% men, 35% with liver cirrhosis. Most were infected with HCV genotype (GT) 1 or 3. The most common prior DAA combinations were sofosbuvir plus an NS5A inhibitor or ombitasvir/paritaprevir/r+dasabuvir. A total of 136 (99%) patients achieved undetectable HCV RNA at the end of treatment. Overall SVR12 was 95% in the 135 patients reaching this point. SVR12 was lower in patients with cirrhosis (89%, p = 0.05) and those with GT3 infection (80%, p <0.001). Patients with GT3 infection and cirrhosis had the lowest SVR12 rate (69%). Of the patients who did not achieve SVR12, 1 was reinfected and 7 experienced treatment failure (6 GT3, 1 GT1a). The presence of resistance-associated substitutions did not impact SVR12. Adverse effects were mild and non-specific. CONCLUSION: Real-world data show that SOF/VEL/VOX is an effective, safe rescue therapy for patients with prior DAA treatment failure despite the presence of resistance-associated substitutions. However, patients with liver cirrhosis infected by GT3 remain the most-difficult-to-treat group. LAY SUMMARY: Treatment with sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) for 12 weeks is the current recommendation for the 5% of patients infected with HCV who do not achieve eradication of the virus under treatment with direct-acting antivirals. In a Spanish cohort of 137 patients who failed a previous combination of direct-acting antivirals, a cure rate of 95% was achieved with SOF/VEL/VOX. Genotypic characteristics of the virus (genotype 3) and the presence of cirrhosis were factors that decreased the rate of cure. Treatment with SOF/VEL/VOX is an effective and safe rescue therapy due to its high efficacy and very good safety profile.
Authors: Mark W Douglas; Enoch S E Tay; Dao Sen Wang; Adrian T L Ong; Caroline Wilson; Amy Phu; Jen Kok; Dominic E Dwyer; Rowena A Bull; Andrew R Lloyd; Tanya L Applegate; Gregory J Dore; Anita Y Howe; Richard Harrigan; Jacob George Journal: Hepatol Commun Date: 2020-04-06
Authors: Sara Cuesta-Sancho; Mercedes Márquez-Coello; Francisco Illanes-Álvarez; Denisse Márquez-Ruiz; Ana Arizcorreta; Fátima Galán-Sánchez; Natalia Montiel; Manuel Rodriguez-Iglesias; José-Antonio Girón-González Journal: World J Hepatol Date: 2022-01-27
Authors: Anita Y M Howe; Chaturaka Rodrigo; Evan B Cunningham; Mark W Douglas; Julia Dietz; Jason Grebely; Stephanie Popping; Javier Alejandro Sfalcin; Milosz Parczewski; Christoph Sarrazin; Adolfo de Salazar; Ana Fuentes; Murat Sayan; Josep Quer; Midori Kjellin; Hege Kileng; Orna Mor; Johan Lennerstrand; Slim Fourati; Velia Chiara Di Maio; Vladimir Chulanov; Jean-Michel Pawlotsky; P Richard Harrigan; Francesca Ceccherini-Silberstein; Federico Garcia Journal: JHEP Rep Date: 2022-02-24
Authors: Eleanor Barnes; Michael Pavlides; Arjun N A Jayaswal; Christina Levick; Jane Collier; Elizabeth M Tunnicliffe; Matthew D Kelly; Stefan Neubauer Journal: Abdom Radiol (NY) Date: 2020-11-28