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 >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.
Subject(s)
Carbamates , Carcinoma, Hepatocellular , Hepacivirus , Hepatitis C, Chronic , Heterocyclic Compounds, 4 or More Rings , Liver Cirrhosis , Liver Neoplasms , Macrocyclic Compounds , Sofosbuvir , Sulfonamides , Antiviral Agents/administration & dosage , Antiviral Agents/adverse effects , Carbamates/administration & dosage , Carbamates/adverse effects , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/etiology , Carcinoma, Hepatocellular/pathology , Drug Combinations , Drug Resistance, Viral , Female , Hepacivirus/drug effects , Hepacivirus/genetics , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/epidemiology , Hepatitis C, Chronic/virology , Heterocyclic Compounds, 4 or More Rings/administration & dosage , Heterocyclic Compounds, 4 or More Rings/adverse effects , Humans , Italy/epidemiology , Liver Cirrhosis/diagnosis , Liver Cirrhosis/epidemiology , Liver Neoplasms/epidemiology , Liver Neoplasms/etiology , Liver Neoplasms/pathology , Macrocyclic Compounds/administration & dosage , Macrocyclic Compounds/adverse effects , Male , Middle Aged , RNA, Viral/isolation & purification , Retreatment/methods , Risk Factors , Sofosbuvir/administration & dosage , Sofosbuvir/adverse effects , Sulfonamides/administration & dosage , Sulfonamides/adverse effects , Sustained Virologic Response , Treatment Outcome , Viral Nonstructural ProteinsABSTRACT
BACKGROUND/AIMS: The aim of the present, open-labeled, randomized study was to determine the efficacy and safety of different doses of consensus interferon plus ribavirin in the initial treatment of chronic hepatitis C. METHODS: One hundred and one genotype 2/3 patients were randomized to receive 9 mcg (group A, n=48) or 18 mcg (group B, n=53) of consensus interferon thrice weekly plus ribavirin (1000/1200 mg/daily) for 24 weeks and 92 genotype 1 patients to receive 9 mcg (group C, n=47) or 18 mcg (group D, n=45) of consensus interferon plus ribavirin for 48 weeks. RESULTS: In an intention-to-treat analysis, the sustained virologic response at 24-week follow-up was 69% and 66% for group A and B (P=0.77) and 40% and 36% for group C and D (P=0.63). The overall sustained response was 67% and 38% in patients with genotype 2/3 and 1, respectively. Among genotype 1 patients the sustained virologic response was 39% and 41% for high or low baseline viremia levels. CONCLUSIONS: Higher consensus interferon dose does not increase sustained virologic response. Naive genotype 1 patients may achieve significant response rate of approximately 40% if treated with 9 mcg of consensus interferon plus ribavirin for 48 weeks.