RESUMEN
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 >13â¯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 12â¯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 (pâ¯=â¯0.005) and hepatocellular carcinoma (pâ¯=â¯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.
Asunto(s)
Carbamatos , Carcinoma Hepatocelular , Hepacivirus , Hepatitis C Crónica , Compuestos Heterocíclicos de 4 o más Anillos , Cirrosis Hepática , Neoplasias Hepáticas , Compuestos Macrocíclicos , Sofosbuvir , Sulfonamidas , Antivirales/administración & dosificación , Antivirales/efectos adversos , Carbamatos/administración & dosificación , Carbamatos/efectos adversos , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/patología , Combinación de Medicamentos , Farmacorresistencia Viral , Femenino , Hepacivirus/efectos de los fármacos , Hepacivirus/genética , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/epidemiología , Hepatitis C Crónica/virología , Compuestos Heterocíclicos de 4 o más Anillos/administración & dosificación , Compuestos Heterocíclicos de 4 o más Anillos/efectos adversos , Humanos , Italia/epidemiología , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/epidemiología , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/patología , Compuestos Macrocíclicos/administración & dosificación , Compuestos Macrocíclicos/efectos adversos , Masculino , Persona de Mediana Edad , ARN Viral/aislamiento & purificación , Retratamiento/métodos , Factores de Riesgo , Sofosbuvir/administración & dosificación , Sofosbuvir/efectos adversos , Sulfonamidas/administración & dosificación , Sulfonamidas/efectos adversos , Respuesta Virológica Sostenida , Resultado del Tratamiento , Proteínas no Estructurales ViralesRESUMEN
BACKGROUND AND AIMS: The efficacy and safety of glecaprevir/pibrentasvir (G/P) for patients infected with hepatitis C virus (HCV) have only been investigated in clinical trials, with no real-world data currently available. The aim of our study was to investigate the effectiveness and safety of G/P in a real-world setting. METHODS: All patients with HCV consecutively starting G/P between October 2017 and January 2018 within the NAVIGATORE-Lombardia Network were analyzed. G/P was administered according to drug label (8, 12 or 16â¯weeks). Fibrosis was staged either histologically or by liver stiffness measurement. Sustained virological response (SVR) was defined as undetectable HCV-RNA 12â¯weeks after the end of treatment. RESULTS: A total of 723 patients (50% males) were treated with G/P, 89% for 8â¯weeks. The median age of our cohort was 58â¯years, with a median body mass index of 23.9â¯kg/m2, and median liver stiffness measurement of 6.1â¯kPa; 84% were F0-2 and 16% were interferon-experienced. Median HCV-RNA was 1,102,600â¯IU/ml, and 49% of patients had HCV genotype 1 (32% 1b), 28% genotype 2, 10% genotype 3 and 13% genotype 4. The median estimated glomerular filtration rate was 90.2â¯ml/min, platelet count 209x103/mm3 and albumin 4.3â¯g/dl. The SVR rates were 94% in intention-to-treat and 99.3% in per protocol analysis (8-week vs. 12 or 16-week: 99.2% vs. 100%). Five patients failed therapy because of post-treatment relapse; a post-treatment NS5A resistance-associated substitution was detected in 1 case. SVR rates were lower in males (p = 0.002) and in HCV genotype-3 (p = 0.046) patients treated for 8â¯weeks, but independent of treatment duration, fibrosis stage, baseline HCV-RNA, HIV co-infection, chronic kidney disease stage and viral kinetics. Mild adverse events were reported in 8.3% of the patients, and 0.7% of them prematurely withdrew treatment. Three patients died of drug-unrelated causes. CONCLUSIONS: In a large real-world cohort of Italian patients, we confirmed the excellent effectiveness and safety of G/P administered for 8, 12 or 16â¯weeks. LAY SUMMARY: A large number of patients with hepatitis C virus have been treated with glecaprevir/pibrentasvir (G/P) within the NAVIGATORE-Lombardia Network, in Italy. This is the first real-world study evaluating effectiveness and safety of G/P in patients with hepatitis C virus treated according to international recommendations. This study demonstrated excellent effectiveness (with sustained virological response rates of 99.3%) and safety profiles.
Asunto(s)
Bencimidazoles , Hepatitis C Crónica , Hígado/patología , Quinoxalinas , Sulfonamidas , Ácidos Aminoisobutíricos , Antivirales/administración & dosificación , Antivirales/efectos adversos , Bencimidazoles/administración & dosificación , Bencimidazoles/efectos adversos , Biopsia/métodos , Estudios de Cohortes , Ciclopropanos , Combinación de Medicamentos , Diagnóstico por Imagen de Elasticidad/métodos , Femenino , Hepacivirus/efectos de los fármacos , Hepacivirus/genética , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/epidemiología , Humanos , Italia/epidemiología , Lactamas Macrocíclicas , Leucina/análogos & derivados , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/etiología , Masculino , Persona de Mediana Edad , Prolina/análogos & derivados , Pirrolidinas , Quinoxalinas/administración & dosificación , Quinoxalinas/efectos adversos , ARN Viral/análisis , Sulfonamidas/administración & dosificación , Sulfonamidas/efectos adversos , Respuesta Virológica Sostenida , Resultado del TratamientoRESUMEN
BACKGROUND: Sofosbuvir (SOF)-based regimens have been associated with renal function worsening in HCV patients with estimated glomerular filtration rate (eGFR)â¯≤â¯45â¯ml/min, but further investigations are lacking. AIM: To assess renal safety in a large cohort of DAA-treated HCV patients with any chronic kidney disease (CKD). METHODS: All HCV patients treated with DAA in Lombardy (December 2014-November 2017) with available kidney function tests during and off-treatment were included. RESULTS: Among 3264 patients [65% males, 67% cirrhotics, eGFR 88 (9-264)â¯ml/min], CKD stage was 3 in 9.5% and 4/5 in 0.7%. 79% and 73% patients received SOF and RBV, respectively. During DAA, eGFR declined in CKD-1 (pâ¯<â¯0.0001) and CKD-2 (pâ¯=â¯0.0002) patients, with corresponding rates of CKD stage reduction of 25% and 8%. Conversely, eGFR improved in lower CKD stages (pâ¯<â¯0.0001 in CKD-3a, pâ¯=â¯0.0007 in CKD-3b, pâ¯=â¯0.024 in CKD-4/5), with 33-45% rates of CKD improvement. Changes in eGFR and CKD distribution persisted at SVR. Baseline independent predictors of CKD worsening at EOT and SVR were age (pâ¯<â¯0.0001), higher baseline CKD stages (pâ¯<â¯0.0001) and AH (pâ¯=â¯0.010 and pâ¯<â¯0.0001, respectively). CONCLUSIONS: During DAA, eGFR significantly declined in patients with preserved renal function and improved in those with lower CKD stages, without reverting upon drug discontinuation.