2026-04-17T17:30:20Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/111022025-10-24T10:31:37Zcom_2072_378070com_2072_378040col_2072_378092

00925njm 22002777a 4500 dc Graf, Christiana author D'Ambrosio, Roberta author Degasperi, Elisabetta author Paolucci, Stefania author Llaneras Artigues, Jordi author Vermehren, Johannes author Buti Ferret, Maria author 2024-02-22T10:29:06Z 2024-02-22T10:29:06Z 2024-03 Hepatitis C virus; Voxilaprevir Virus de l'hepatitis C; Voxilaprevir Virus de la hepatitis C; Voxilaprevir Background & Aims Voxilaprevir/velpatasvir/sofosbuvir (VOX/VEL/SOF) is highly effective for re-treatment of direct-acting antiviral (DAA)-experienced patients with chronic HCV infection. In the present study, predictors of virologic treatment response were analyzed in an integrative analysis of three large real-world cohorts. Methods Consecutive patients re-treated with VOX/VEL/SOF after DAA failure were enrolled between 2016 and 2021 in Austria, Belgium, Germany, Italy, Spain and Switzerland. Results A total of 746 patients were included: median age was 56 (16-88) years and 77% were male. Most patients were infected with HCV genotype 1 (56%) and 3 (32%). 86% of patients carried resistance-associated substitutions in the NS3, NS5A or NS5B regions. Overall, 95.4% (683/716) of patients achieved a sustained virologic response. Treatment effectiveness was significantly affected by advanced liver disease (p <0.001), hepatocellular carcinoma (p <0.001), higher baseline ALT levels (p = 0.02), HCV genotype 3 (p <0.001), and prior VEL/SOF treatment (p = 0.01). In a multivariate analysis, only HCV genotype 3, hepatocellular carcinoma and cirrhosis turned out to be independent predictors of treatment failure. Resistance-associated substitutions, as well as the presence of rare genotypes, did not impact treatment outcome. The effectiveness of rescue therapy with glecaprevir/pibrentasvir and SOF, with or without ribavirin, for 12 to 24 weeks was found to be high (100%). Conclusions Infection with HCV genotype 3, the presence of liver cancer and cirrhosis are independently associated with failure of VOX/VEL/SOF re-treatment. It is unclear whether the addition of ribavirin and/or extension of treatment duration may be effective to avoid virologic relapse on VOX/VEL/SOF. However, rescue treatment with glecaprevir/pibrentasvir+SOF seems to be effective. Impact and implications Representative data on the effectiveness of voxilaprevir/velpatasvir/sofosbuvir (VOX/VEL/SOF) in clinical practice are still scarce and the collection of a larger number of patients with difficult-to-treat cofactors including the assessment of resistance-associated substitution profiles is required before more specific recommendations for optimal re-treatment in these patients can be given. Thus, we aimed to analyze treatment effectiveness and predictors of virologic response to VOX/VEL/SOF in an integrative analysis of three large real-word cohorts. The study results, derived from a multicenter cohort consisting of 746 patients, demonstrated that re-treatment with VOX/VEL/SOF is an effective salvage therapy associated with an overall per protocol sustained virologic response rate of 95%. Hepatocellular carcinoma onset, cirrhosis and HCV genotype 3 were identified as independent negative predictors of treatment response, whereas resistance-associated substitutions, as well as rare genotypes and chimera, did not impact sustained virologic response rates following re-treatment with VOX/VEL/SOF. This study was supported by a DZIF (German Center for Infection Research) grant entitled ‘HCV Treatment Optimization’ to CS and JD (TTU 05.809). http://hdl.handle.net/11351/11102 Hepatitis C - Tractament Medicaments antivírics - Ús terapèutic DISEASES::Digestive System Diseases::Liver Diseases::Hepatitis::Hepatitis, Chronic::Digestive System Diseases::Liver Diseases::Hepatitis::Hepatitis C, Chronic CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiviral Agents ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Retreatment ENFERMEDADES::enfermedades del sistema digestivo::enfermedades hepáticas::hepatitis::hepatitis crónica::enfermedades del sistema digestivo::enfermedades hepáticas::hepatitis::hepatitis C crónica COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antiinfecciosos::antivíricos TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::retratamiento Real-world effectiveness of voxilaprevir/velpatasvir/sofosbuvir in patients following DAA failure