Elisabetta Degasperi1, Angiola Spinetti2, Andrea Lombardi3, Simona Landonio4, Maria Cristina Rossi5, Luisa Pasulo6, Pietro Pozzoni7, Alessia Giorgini8, Paolo Fabris9, Antonietta Romano10, Lorenzo Lomonaco11, Massimo Puoti12, Maria Vinci13, Federico Gatti14, Giada Carolo15, Alessia Zoncada16, Paolo Bonfanti17, Francesco Paolo Russo18, Alessio Aghemo19, Alessandro Soria20, Riccardo Centenaro21, Franco Maggiolo6, Pierangelo Rovere22, Francesca Pasin23, Veronica Paon24, Giovanni Faggiano25, Alessandro Vario26, Glenda Grossi27, Roberta Soffredini28, Canio Carriero2, Stefania Paolucci29, Franco Noventa30, Alfredo Alberti23, Pietro Lampertico28, Stefano Fagiuoli6. 1. CRC A.M. e A. Migliavacca Center for Liver Diseases, Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy. Electronic address: elisabetta.degasperi@unimi.it. 2. Infectious Diseases, ASST Spedali Civili Brescia, Brescia, Italy. 3. Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy. 4. Infectious Diseases, Sacco Hospital, Milan, Italy. 5. Infectious Diseases, Treviso Hospital, Treviso, Italy. 6. Bergamo HCV Network, ASST Papa Giovanni XXIII, Italy. 7. Internal Medicine, ASST Lecco Hospital (LC), Italy. 8. Gastroenterology and Hepatology, ASST Santi Paolo e Carlo, Milan, Italy. 9. Infectious Diseases, Santorso Hospital, Vicenza, Italy. 10. Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy. 11. Gastroenterology, Bussolengo Hospital, Verona, Italy. 12. Infectious Diseases, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy. 13. Gastroenterology and Hepatology, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy. 14. Hospital Pharmacy, ASST Ovest Milanese, Legnano (MI), Italy. 15. Infectious Diseases, University of Verona, Verona, Italy. 16. Infectious Diseases, ASST Cremona, Cremona (CR), Italy. 17. Infectious Diseases, ASST Lecco Hospital (LC), Italy. 18. Gastroenterology and Multivisceral Transplant, University Hospital Padua, Padova, Italy. 19. Internal Medicine and Hepatology, IRCCS Humanitas Research Hospital, Humanitas University, Pieve Emanuele (MI), Italy. 20. Infectious Diseases, San Gerardo Hospital, ASST Monza, Monza (MB), Italy. 21. Internal Medicine, ASST Melegnano Martesana, Vizzolo Predabissi (MI), Italy. 22. Infectious Diseases, Legnago Hospital, Verona, Italy. 23. Department of Molecular Medicine, University of Padova, Padova, Italy. 24. Internal Medicine, University of Verona, Verona, Italy. 25. Infectious Diseases, Rovigo Hospital, Italy. 26. Hepatology, ULSS 17 Veneto Hospital, Este (PD), Italy. 27. Internal Medicine, ASST Ovest Milanese, Magenta Hospital (MI), Italy. 28. CRC A.M. e A. Migliavacca Center for Liver Diseases, Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy. 29. Molecular Virology Unit, Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. 30. QUOVADIS no profit Association.
Abstract
BACKGROUND & AIMS: Sofosbuvir/velpatasivr/voxilaprevir (SOF/VEL/VOX) is approved for retreatment of patients with HCV and a previous failure on direct-acting antivirals (DAAs), however real-life data are limited. The aim of this study was to assess the effectiveness and safety of SOF/VEL/VOX in a real-life setting. METHODS: All consecutive patients with HCV receiving SOF/VEL/VOX between May-October 2018 in 27 centers in Northern Italy were enrolled. Bridging fibrosis (F3) and cirrhosis (F4) were diagnosed by liver stiffness measurement: >10 and >13 kPa respectively. Sustained virological response (SVR) was defined as undetectable HCV-RNA 4 (SVR4) or 12 (SVR12) weeks after the end-of-treatment. RESULTS: A total of 179 patients were included: median age 57 (18-88) years, 74% males, median HCV-RNA 1,081,817 (482-25,590,000) IU/ml. Fibrosis stage was F0-F2 in 32%, F3 in 21%, F4 in 44%. HCV genotype was 1 in 58% (1b 33%, 1a 24%, 1nc 1%), 2 in 10%, 3 in 23% and 4 in 9%; 82% of patients carried resistance-associated substitutions in the NS3, NS5A or NS5B regions. Patients received SOF/VEL/VOX for 12 weeks, ribavirin was added in 22% of treatment schedules. Undetectable HCV-RNA was achieved by 74% of patients at week 4 and by 99% at week 12. Overall, 162/179 (91%) patients by intention to treat analysis and 162/169 (96%) by per protocol analysis achieved SVR12, respectively; treatment failures included 6 relapsers and 1 virological non-responder. Cirrhosis (p = 0.005) and hepatocellular carcinoma (p = 0.02) were the only predictors of treatment failure. Most frequent adverse events included fatigue (6%), hyperbilirubinemia (6%) and anemia (4%). CONCLUSIONS: SOF/VEL/VOX is an effective and safe retreatment for patients with HCV who have failed on a previous DAA course in a real-life setting. LAY SUMMARY: This is the largest European real-life study evaluating effectiveness and safety of sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) in a large cohort of consecutive patients with hepatitis C virus infection and a prior direct-acting antiviral failure, who were treated within the NAVIGATORE Lombardia and Veneto Networks, in Italy. This study demonstrated excellent effectiveness (98% and 96% sustained virological response rates at week 4 and 12, respectively) and an optimal safety profile of SOF/VEL/VOX. Cirrhosis and hepatocellular carcinoma onset were the only features associated with treatment failure.
BACKGROUND & AIMS:Sofosbuvir/velpatasivr/voxilaprevir (SOF/VEL/VOX) is approved for retreatment of patients with HCV and a previous failure on direct-acting antivirals (DAAs), however real-life data are limited. The aim of this study was to assess the effectiveness and safety of SOF/VEL/VOX in a real-life setting. METHODS: All consecutive patients with HCV receiving SOF/VEL/VOX between May-October 2018 in 27 centers in Northern Italy were enrolled. Bridging fibrosis (F3) and cirrhosis (F4) were diagnosed by liver stiffness measurement: >10 and >13 kPa respectively. Sustained virological response (SVR) was defined as undetectable HCV-RNA 4 (SVR4) or 12 (SVR12) weeks after the end-of-treatment. RESULTS: A total of 179 patients were included: median age 57 (18-88) years, 74% males, median HCV-RNA 1,081,817 (482-25,590,000) IU/ml. Fibrosis stage was F0-F2 in 32%, F3 in 21%, F4 in 44%. HCV genotype was 1 in 58% (1b 33%, 1a 24%, 1nc 1%), 2 in 10%, 3 in 23% and 4 in 9%; 82% of patients carried resistance-associated substitutions in the NS3, NS5A or NS5B regions. Patients received SOF/VEL/VOX for 12 weeks, ribavirin was added in 22% of treatment schedules. Undetectable HCV-RNA was achieved by 74% of patients at week 4 and by 99% at week 12. Overall, 162/179 (91%) patients by intention to treat analysis and 162/169 (96%) by per protocol analysis achieved SVR12, respectively; treatment failures included 6 relapsers and 1 virological non-responder. Cirrhosis (p = 0.005) and hepatocellular carcinoma (p = 0.02) were the only predictors of treatment failure. Most frequent adverse events included fatigue (6%), hyperbilirubinemia (6%) and anemia (4%). CONCLUSIONS:SOF/VEL/VOX is an effective and safe retreatment for patients with HCV who have failed on a previous DAA course in a real-life setting. LAY SUMMARY: This is the largest European real-life study evaluating effectiveness and safety of sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) in a large cohort of consecutive patients with hepatitis C virus infection and a prior direct-acting antiviral failure, who were treated within the NAVIGATORE Lombardia and Veneto Networks, in Italy. This study demonstrated excellent effectiveness (98% and 96% sustained virological response rates at week 4 and 12, respectively) and an optimal safety profile of SOF/VEL/VOX. Cirrhosis and hepatocellular carcinoma onset were the only features associated with treatment failure.
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: Paweł Pabjan; Michał Brzdęk; Magdalena Chrapek; Kacper Dziedzic; Krystyna Dobrowolska; Katarzyna Paluch; Anna Garbat; Piotr Błoniarczyk; Katarzyna Reczko; Piotr Stępień; Dorota Zarębska-Michaluk Journal: Viruses Date: 2022-01-06 Impact factor: 5.048