Search

Direct-acting antivirals (DAA) regimens have provided hope for eliminating hepatitis C virus (HCV) infection. Patients following ineffective therapy with DAA, especially those previously treated with inhibitors of non-structural protein 5A (NS5A), remain a challenge. The study aimed to assess the effectiveness of DAA pangenotypic options in patients after failure of NS5A containing genotype-specific regimens. The analysis included 120 patients selected from the EpiTer-2 database with data on 15675 HCV-infected individuals treated with IFN-free therapies from 1 July 2015 to 30 June 2022 at 22 Polish hepatology centres. The majority of them were infected with genotype (GT) 1b (85.8%) and one-third was diagnosed with fibrosis F4. Among the rescue pangenotypic regimens, the most commonly used was the sofosbuvir/velpatasvir (SOF/VEL) ± ribavirin (RBV) combination. The sustained virologic response, which was a measure of treatment effectiveness, was achieved by 102 patients, resulting in cure rate of 90.3% in the per protocol analysis. All 11 non-responders were infected with GT1b, 7 were diagnosed with cirrhosis, and 9 were treated with SOF/VEL±RBV. We demonstrated the high effectiveness of the pangenotypic rescue options in patients after genotype specific NS5A-containing regimens failures, identifying cirrhosis as a negative prognostic factor of treatment effectiveness. [ABSTRACT FROM AUTHOR]

Introduction: Non-cirrhotic treatment-naive hepatitis C patients infected with genotype 1 can be treated with ledipasvir/sofosbuvir (LDV/SOF) for 8 weeks, but in practice this regimen is frequently extended up to 12 weeks at least in part due to insufficient real-world data supporting shortening of treatment. The aim of our study was to compare 8- and 12-week regimens’ efficacy in patients eligible for 8-week therapy in a real-world setting. Material and methods: Data of HCV genotype 1 infected patients treated with LDV/SOF between 2015 and 2018 included in the EpiTer-2 database were analyzed with respect to patients’ characteristics and length of treatment. Results: Among a total of 1718 patients treated with LDV/SOF, 679 were included in the analysis, 238 (35%) received 8-week regimen, whereas 441 were treated for 12 weeks although they fulfilled the criteria for a shorter course. The majority of patients were infected with genotype 1b (89%) and demonstrated minimal fibrosis (55%). The 12-week regimen was assigned significantly more frequently to patients with comorbidities, concomitant medications and advanced liver fibrosis. The sustained virologic response rate was similar after 8 (98%) and 12 (97%) weeks of therapy according to intent-to-treat analysis and reached 99% in both groups after exclusion of patients lost to follow-up. Conclusions: We confirmed high effectiveness regardless of treatment duration with LDV/SOF in non-cirrhotics infected with HCV genotype 1 eligible for the 8-week regimen according to the current label. This real-world study also demonstrated no need for addition of ribavirin (RBV) in this population and showed that shortening of treatment significantly improves the safety profile of LDV/SOF medication. [ABSTRACT FROM AUTHOR]

Background and Aims: The revolution of the antiviral treatment of hepatitis C virus (HCV) infection resulting in higher effectiveness came with the introduction of direct‐acting antivirals with pangenotypic regimens as a final touch. Among them, the combination of glecaprevir (GLE) and pibrentasvir (PIB) provides the opportunity for shortening therapy to 8 weeks in the majority of patients. Because of still insufficient evaluation of this regimen in the real‐world experience, our study aimed to assess the efficacy and safety of 8‐week GLE/PIB in chronic hepatitis C patients depending on liver fibrosis and genotype (GT). Methods: The analysis included patients who received GLE/PIB for 8 weeks selected from the EpiTer‐2 database, large retrospective national real‐world study evaluating antiviral treatment in 12 584 individuals in 22 Polish hepatology centers. Results: A total of 1034 patients with female predominance (52%) were enrolled in the analysis. The majority of them were treatment naïve (94%), presented liver fibrosis (F) of F0–F3 (92%), with the most common GT1b, followed by GT3. The overall sustained virologic response after exclusion of nonvirologic failures was achieved in 95.8% and 98%, respectively (P = 0.19). In multivariate logistic regression HCV GT‐3 (beta = 0.07, P = 0.02) and HIV infection (beta = −0.14, P < 0.001) were independent predictors of nonresponse. Conclusions: We demonstrated high effectiveness of 8‐week GLE/PIB treatment in a non‐GT3 population irrespective of liver fibrosis stage. Comparable efficacy was achieved in non‐cirrhotic patients regardless of the genotype, including GT3 HCV. [ABSTRACT FROM AUTHOR]

Background and Aim: Grazoprevir/elbasvir (GZR/EBR) was approved for the treatment of chronic hepatitis C virus (HCV) genotype 1 and 4 infected patients with or without compensated liver cirrhosis. The aim of this study was to assess GZR/EBR regimen in the real‐world experience, particularly in previously "difficult‐to‐treat" patients with chronic kidney diseases, human immunodeficiency virus‐coinfected, cirrhotics, and treatment‐experienced. Methods: The analysis included patients treated with GZR/EBR selected from 10 152 individuals from the EpiTer‐2 database, large national real‐world study evaluating antiviral treatment in 22 Polish hepatology centers between 2015 and 2018. Data were completed retrospectively and submitted online. Results: A total of 1615 patients who started GZR/EBR therapy in 2017 and 2018 with a female predominance (54%) and median age of 54 years were analyzed. The majority were infected with GT1b (89%) and treatment naïve (81%). Liver cirrhosis was diagnosed in 19%, and 70% of patients had comorbidities, of which chronic renal disease was present in 7% and HIV‐coinfection in 4%. Overall, a sustained virologic response (SVR) was achieved by 95% according to intent‐to‐treat (ITT) and 98% after exclusion of lost to follow up (modified ITT). No differences were found in cure rate between all included patients and subpopulations previously considered as difficult‐to‐treat. Majority of patients completed the treatment course as scheduled, adverse events were mostly mild and did not lead to therapy discontinuation. Conclusions: GZR/EBR treatment carried‐out in patients infected with HCV genotype 1 and 4 demonstrated good tolerability and an excellent SVR rate with no effectiveness reduction in so called difficult‐to‐treat populations. [ABSTRACT FROM AUTHOR]

Ruzasvir (MK‐8408, an NS5A inhibitor) and uprifosbuvir (MK‐3682, a nonstructural protein 5B nucleotide inhibitor) are highly potent direct‐acting antiviral agents for the treatment of hepatitis C virus (HCV) infection. A phase III clinical trial evaluating the two‐drug combination of ruzasvir 60 mg plus  uprifosbuvir 450 mg suggested suboptimal efficacy in certain HCV genotypes (C‐BREEZE 1; NCT02759315). The aim of the present study was to evaluate the efficacy and safety of ruzasvir in combination with uprifosbuvir administered at a higher dose than that assessed in the earlier study (C‐BREEZE 2: NCT02956629/Merck protocol PN041). Treatment‐naïve or interferon (with or without ribavirin)‐experienced participants with or without compensated cirrhosis were enrolled. All participants received ruzasvir 180 mg plus uprifosbuvir 450 mg once daily for 12 weeks. The primary objectives were the proportion of participants with HCV RNA <15 lU/mL at 12 weeks after the end of study therapy (SVR12), and safety and tolerability of the study drug. Overall, 282 participants were enrolled. SVR12 (n/N) was 91.3% (42/46) in participants infected with HCV genotype (GT) 1a; GT1b, 96.7% (29/30); GT2, 91.5% (43/47); GT3, 73.8% (45/61); GT4, 98.2% (55/56); GT5, 100.0% (18/18); and GT6, 90.9% (20/22). Adverse events (AEs) were reported by 61.3% of participants; drug‐related AEs were reported by 33.3%. The most frequent (≥5% of participants) drug‐related AEs in all participants were fatigue (7.8%) and headache (7.4%). In conclusion, the two‐drug combination of ruzasvir 180 mg plus uprifosbuvir 450 mg for 12 weeks was highly effective and well tolerated in participants infected with HCV GT1, GT2, GT4, GT5 and GT6, with a lower efficacy in GT3‐infected persons. [ABSTRACT FROM AUTHOR]

Aim of the study: This multicentre study aimed to examine the actual risk for drug-drug interactions in a cohort of Polish patients, and their impact on antiviral therapy. Material and methods: Concomitant medications were analyzed in hepatitis C virus (HCV)-infected patients treated with still valuable therapy with OBV/PTV/r ± DSV ± RBV. An established online tool (http://www. hep-druginteractions.org/) was used to assess potential drug interactions. To assess the impact of comedications on virologic outcomes, HCV RNA levels were measured at given time points during and after the treatment. The results were compared between subgroups depending on the number of drugs used. Results: Among the 209 patients included in this multicentre study, concomitant medications were taken by 140 (67.0%) patients. Modification of treatment due to expected interactions was required in 33 (15.8%) patients, of whom nine (4.3%) had at least one comedication replaced or discontinued. Sustained virologic response rates ranged from 95.1% to 100.0%, and were lowest in patients taking one to five comedications who were null-responders to pegylated interferon or cirrhotic. Conclusions: Although most HCV-infected patients received concomitant medications, only some required treatment modification. OBV/PTV/r ± DSV ± RBV was effective in all subgroups, irrespective of the number of comedications taken. Multimorbidity and polypharmacy in patients with chronic hepatitis C should not discourage the decision to initiate antiviral therapy, although caution should be exercised for potential drug-drug interactions. [ABSTRACT FROM AUTHOR]

Background: International guidelines recommend treatment of hepatitis C virus (HCV) infection in people who inject drugs (PWID), including those on opioid substitution therapy (OST). The pangenotypic combination of glecaprevir and pibrentasvir has shown high sustained virologic response at post-treatment Week 12 (SVR12) in clinical trials. Herein, we evaluate the safety and efficacy of glecaprevir/pibrentasvir in patients receiving OST.Methods: Pooled data from patients with HCV genotypes 1-6 who were treated with glecaprevir/pibrentasvir for 8, 12, or 16 weeks in eight Phase 2 and 3 trials were categorized by use of OST. Treatment completion, treatment adherence, SVR12, adverse events (AEs), and laboratory abnormalities were evaluated for patients receiving and not receiving OST.Results: Among 2256 patients, 157 (7%) were receiving OST. Compared with patients not receiving OST, OST patients were younger (mean age, 46.8 vs 52.8 years), male (69% vs 54%), white (93% vs 80%), HCV treatment-naïve (86% vs 72%), had HCV genotype 3 (60% vs 26%), and had a history of depression or bipolar disorder (43% vs 19%). Most patients completed (OST: 98% [n/N = 154/157]; non-OST: 99% [n/N = 2070/2099]) and were adherent (received ≥90% of study drug doses) to glecaprevir/pibrentasvir treatment (OST: 98% [n/N = 121/123]; non-OST: 99% [n/N = 1884/1905] among patients with available data). In the intention-to-treat population, SVR12 rates in OST and non-OST patients were 96.2% (n/N = 151/157; 95% CI 93.2-99.2) and 97.9% (n/N = 2055/2099; 95% CI 97.3-98.5), respectively. For OST patients, reasons for nonresponse included virologic relapse (<1%; n = 1), premature study drug discontinuation (<1%; n = 1), and loss to follow-up (3%; n = 4). AEs occurring in ≥10% of OST patients were headache, fatigue, and nausea. Drug-related serious AEs, AEs leading to study drug discontinuation, and Grade 3 or higher laboratory abnormalities were infrequent in both groups (<1%). No HCV reinfections occurred through post-treatment Week 12.Conclusion: Glecaprevir/pibrentasvir is highly efficacious and well tolerated in HCV-infected patients receiving OST. [ABSTRACT FROM AUTHOR]

Background: Injection drug use is the primary mode of transmission for hepatitis C virus (HCV), and treatment guidelines recommend treating HCV-infected people who use drugs; however, concerns about adherence, effectiveness, and reinfection have impeded treatment uptake.Methods: Data were pooled from seven phase III trials that evaluated the efficacy and safety of 8 or 12 weeks of glecaprevir/pibrentasvir (G/P) in patients chronically infected with HCV genotypes 1-6. Patients had compensated liver disease, with or without cirrhosis, and were HCV treatment-naïve or -experienced with interferon or pegylated interferon ± ribavirin, or sofosbuvir plus ribavirin ± pegylated interferon. Patients were grouped into recent drug users (injection drug use ≤12 months before screening, positive urine drug screen [UDS], and/or drug-related adverse event), former drug users (>12 months before screening and negative UDS), or non-drug users. Assessments included sustained virologic response at 12 weeks posttreatment (SVR12), treatment adherence, and safety.Results: Among 1819 patients, 5%, 34%, and 61% were recent, former, and non-drug users, respectively. Treatment adherence and completion were high (≥96%) regardless of drug use status. SVR12 was achieved by 93% (n/N = 91/98), 97% (n/N = 591/610), and >99% (n/N = 1106/1111) of recent, former, and non-drug users, respectively (intention-to-treat analysis). The overall rates of virologic failure were ≤1.5% across all three subpopulations, with no HCV reinfections among recent drug users. Drug-related serious adverse events and adverse events leading to treatment discontinuation were experienced by ≤1% of patients.Conclusions: G/P is a well-tolerated and efficacious pangenotypic regimen for chronic HCV-infected people with recent or active drug use. [ABSTRACT FROM AUTHOR]

Background: In the interferon era, patients with HCV-related cirrhosis were considered hard to treat due to contraindications to therapy, safety issues, and poor response. Objectives: We investigated interferon-free regimens in cirrhotic patients in real-world practice. Methods: We analyzed data of HCV infected patients with liver cirrhosis conducted in 22 Polish hepatology centers. They were assigned to a treatment schedule based on physician decision. Data were collected retrospectively by an online questionnaire. Results: In total, 1113 patients infected with genotype 1 HCV were enrolled to the analysis, 96.6% presented GT1b infection. A total of 56% were treatment-experienced, mostly with PegIFN + RBV, 77.2% of group presented comorbidities with the most frequent hypertension and diabetes, 73.2% patients were treated with concomitant medications, and 31% of cohort was assigned to RBV-free regimen, majority of them to OBV/PTV/r + DSV. Overall, 94.7% patients achieved the sustained virological response in intent-to-treat analysis, with comparable rate for RBV-free and RBV-containing options (94.2% vs. 94.9%). Treatment course was more often modified in RBV-containing group, whereas rate of discontinuation was the same for both cohorts. Adverse events were observed in 41% with the most common weakness/fatigue; more frequently in RBV-containing regimens (43% vs. 36.6%). Serious adverse events were reported in 4.1% patients. A total of 16 deaths not related to study drugs were documented, mostly in RBV-containing group. Conclusions: We confirmed effectiveness of the interferon-free regimens without ribavirin in real-world cohort of cirrhotic patients with chronic HCV infection genotype 1. Therapy was well tolerated with infrequent adverse events. [ABSTRACT FROM AUTHOR]