Efficacy and safety of sofosbuvir-based direct-acting antiviral treatment in children and adolescent patients with chronic hepatitis C / 中华传染病杂志

Objective:To explore the efficacy and safety of sofosbuvir-based direct-acting antiviral treatment in children and adolescent patients with chronic hepatitis C (CHC).Methods:A total of 52 children and adolescent patients who admitted to The Third People′s Hospital of Kunming City and The People′s Hospital of Fuyuan County aged from three to 17 years old with CHC from January 2018 to August 2022 were enrolled, and their basic information was collected. Patients were treated with sofosbuvir/velpatasvir (SOF/VEL) or ledipasvir/sofosbuvir (LDV/SOF) with or without ribavirin for 12 weeks. The biochemical and virological indexes were followed up before and after treatment and 12 weeks after withdrawal. The primary endpoint was the sustained virological response (SVR) at week 12 of follow-up after treatment, and the occurrence of adverse events (AE) during treatment. Statistical analysis was used by nonparametric test.Results:A total of 52 patients with CHC including 38 children and 14 adolescents were enrolled. Thirty-one were male and 21 were female. The age was 9(7, 12) years old. Among 52 patients, seven patients were type 1b, 11 were type 2a, three were type 2, five were type 3a, 18 were type 3b, one was type 6a, three were type 6k, four were type 6n and one was type 6v. Twelve (23.1%) patients were vertical transmission, 21(40.4%) patients had horizontal transmission among family members, two (3.8%) patients were blood fluid transmission, and 17(32.7%) were unknown transmission route. Compared with the baseline levels, Total bilirubin, alanine aminotransferase and aspartate aminotransferase were all significantly decreased after 12 weeks of treatment and 12 weeks after withdrawal, and the differences were statistically significant ( F=12.71, 30.23 and 42.52, respectively, all P<0.05). Up to September 30, 2022, 100.0%(52/52) of patients achieved SVR at the end of treatment. For patients who completed follow-up for 12 weeks after treatment, 95.8%(46/48) achieved SVR. Common AEs during treatment were fatigue (11.5%(6/52)), headache (5.8%(3/52)), dizziness (1.9%(1/52)), abdominal pain (3.8%(2/52)), diarrhea (1.9%(1/52)), rash (1.9%(1/52)) and skin pruritus (1.9%(1/52)). No patients discontinued treatment because of AE. Conclusions:Sofosbuvir-based direct-acting antiviral treatment is efficient and well-tolerated in children and adolescent patients with CHC. No patients discontinued treatment due to AE.

Efficacy of Sofosbuvir and Ledipasvir in Comparison to Sofosbuvir and Daclatasvir in Management of Egyptian Chronic Hepatitis C Patients

In Egypt, the prevalence of hepatitis C virus (HCV) antibodies is the highest worldwide by 7.6%. Applying efficient treatment protocol on large scale could decrease HCV prevalence as well as disease burden.The aim of this study is to compare the efficacy of Sofosbuvir plus ledipasvir versus Sofosbuvir plus daclatasvir in management of chronic hepatitis C Egyptian patients with either easy to treat (naive patients with Child score A5)or difficult to treat (interferon experienced).

Efficacy and safety of ledipasvir/sofosbuvir versus elbasvir/grazoprevir in treatment of genotype 1b chronic hepatitis C / 中华临床感染病杂志

Objective:To compare the clinical efficacy and safety of ledipasvir/sofosbuvir (LDV/SOF) and elbasvir/grazoprevir (EBR/GZR) in treatment of patients with chronic hepatitis C (CHC).Methods:The clinical data of 143 patients with genotype 1b CHC treated in Huzhou Central Hospital from January 2020 to December 2021 were retrospectively analyzed, including 74 cases treated with LDV/SOF and 69 cases treated with EBR/GZR. The virological response after 4 and 12 weeks of treatment and 12wk after drug withdrawal was determined; and the serological and liver inflammation indexes before and after treatment in two groups were compared. SPSS 25.0 software was used for statistical analysis of the data.Results:The virological response rates of the LDV/SOF group and EBR/GZR group were 97.30% and 98.55%, 98.65% and 100.00%, 97.30% and 98.55% after 4 and 12 weeks of treatment and 12 weeks after the end of treatment, respectively (all P > 0.05). At the end of treatment, the liver inflammation indexes ALT, AST and GGT in the two groups were significantly lower than the baseline levels ( Z=-7.470 and -6.974, -9.757 and -6.832, -3.578 and -4.054, P<0.01). Adverse reactions in both groups were mild, and no serious adverse events occurred. Conclusion:Both LDV/SOF and EBR/GZR have good clinical efficacy in the treatment of genotype 1b CHC patients. And the patients are well tolerated.

An Innovative Method Development And Forced Degradation Studies For Simultaneous Estimation Of Sofosbuvir And Ledipasvir By Rp Hplc

Objective: To develop an innovative, rapid, simple, cost-effective, stability indicating reverse phase-high performance liquid chromatography (RP-HPLC) method for simultaneous estimation of ledipasvir (LP) and sofosbuvir (SB) in combination pill dosage form. Methods: The method was developed using C8 column, 250 mm x 4.6 mm, 5 mm using mobile section comprising of 0.1% (v/v) orthophosphoric acid buffer at pH 2.2 and acetonitrile in the ratio of 45:55 that was pumped through the column at a flow rate of 0.8 ml/min. Temperature was maintained at 30 °C, the effluents were monitored at 260 nm with the help of usage of PDA detector. Results: The retention time of LP and SB were found to be 2.246 min and 3.502 min. The approach was found to be linear with the variety of 9-36 µg/ml and 40-240 μg/ml for LP and SB respectively, the assay of estimated compounds were found to be 99.65% and 99.73% w/v for LP and SB respectively. Conclusion: The pressured samples changed into analyzed and this proposed a technique turned into determined to be particular and stability indicating as no interfering peaks of decay compound and excipients were observed. Hence, the approach was easy and economical that may be efficiently applied for simultaneous estimation of both LP and SB in bulk and combination tablet system.

Tratamiento exitoso con los nuevos antivirales de acción directa en paciente infectado con el virus de la hepatitis C con fibrosis avanzada y dos recaídas previas: Reporte de caso / Successful treatment with new direct acting antiviral in an infected patient with hepatitis C virus with advanced liver fibrosis in a treatment experienced patient: Case report

El tratamiento del virus de la hepatitis C ha presentado grandes cambios en los últimos años. El esquema base utilizado era Interferón Pegylado y Ribavirina, con el que se lograba respuesta viral sostenida (RVS) de alrededor del 50%. Con la adición de los inhibidores de proteasa Telaprevir y Boceprevir al esquema "esqueleto" de Interferon Pegylado y Ribavirina, la tasa de RVS mejoró hasta valores cercanos a 70%; sin embargo, ocurren efectos colaterales importantes y difícil adherencia. Los nuevos antivirales de acción directa (AAD) (inhibidores de la polimerasa NS5A y NS5B), tienen altas tasas de RVS alcanzando valores mayores de 95% en los diferentes genotipos, en pacientes que recibieron tratamiento previo o no, incluyendo cirróticos. Se presenta el caso de un paciente que recibió dos esquemas terapéuticos previos y con fibrosis hepática avanzada que presentó RVS al ser tratado con los nuevos AAD (Sofosbuvir y Ledipasvir). (AU)

The treatment of hepatitis C virus utilized was Pegylated Interferon and Ribavirin, achieving a sustained virological response (SVR) of about 50 %. With the addition of the first-generation protease inhibitors Telaprevir and Boceprevir to the Pegylated Interferon/Ribavirin backbone the SVR rates rose up to approximately 70%, but with important side effects and a difficult adherence. The new direct acting antivirals (NS5A and NS5B polymerase inhibitors) improved SVR rates to 95 % or greater in the different genotypes, in the treatment-naive and treatment experienced patients including patients with cirrhosis. We report the case of a patient with advanced fibrotic stage, who failed to respond to 2 regimens and was subsequently treated with Ledipasvir/Sofosbuvir and achieved virogical cure. (AU)

Combination of Ledipasvir and Sofosbuvir for Treatment of Hepatitis C Virus Genotype 1 Infection: Systematic Review and Meta-Analysis

ABSTRACT Background and aim. The combination of Sofosbuvir (SOF) and Ledipasvir (LDV) has been lead to considerable enhancement of treatment of hepatitis C virus (HCV) genotype 1 infection. A meta-analysis of the currently available studies was undertaken with the aim to evaluate the antiviral efficacy of SOF/LDV therapy for 12 or 24 weeks with or without Ribavirin (RBV) in patients with HCV genotype 1 infection. Material and methods. In this meta-analysis, we searched databases including PubMed, Scopus, Science Direct and Web of Science using appropriate keywords. All papers which evaluated the efficacy of combination therapy of SOF/LDV with or without RBV for 12 or 24 weeks among patients with HCV genotype 1 infection were included. Results. The 20 published articles were assessed for eligibility and finally 10 articles pooling 2248 participants were included in this meta-analysis. Pooled SVR12 for four SOF/LDV regimens were 95% (95%CI = 93%-97%) for 12 weeks of treatment with SOF/LDV, 97% (95%CI = 95%-98%) for 24 weeks of treatment with SOF/LDV, 96% (95%CI = 94%-97%) for 12 weeks of treatment with SOF/ LDV/RBV and 98% (95%CI = 97%-99%) for 24 weeks of treatment with SOF/LDV/RBV. Only in treatment regimen of SOF/LDV for 12 weeks, cirrhosis had a significant effect on the SVR12 (OR = 0.21, 95%CI = 0.07-0.66). Furthermore, NS5A resistance-associated substitutions at baseline were associated with decrease in the rate of SVR (OR = 0.31, 95%CI = 0.2-0.5). Conclusions. The Interferon-free regimen of SOF/LDV for 12 or 24 weeks with or without RBV is highly effective for treatment of patients with HCV genotype 1 infection.

Determination of Potential Genetoxic Impurity in Ledipasvir by UPLC-MS/MS / 中国药师

Objective: To establish a UPLC-MS/MS method for the determination of the residual quantity of potential genetoxic impurity 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC) in ledipasvir.Methods: The chromatographic conditions were as follows: an Agilent ZORBAX SB-C18 (75 mm×4.6 mm, 3.5 μm) column was used with methanol-0.1% formic acid (50∶50) as the mobile phase.The flow rate was 0.3 ml·min-1.The column temperature was 30 ℃ and the injection volume was 5 μl.The mass spectrometry conditions were as follows: electrospray ionization source (ESI), multistage reaction monitoring (MRM), positive ion scanning mode, ion spray voltage of 2 500 V, ion source temperature of 500 ℃, atomization gas of 379.0 kPa, auxiliary gas of 275.6 kPa, curtain gas of 137.8 kPa, collision gas of 41.3 kPa, ion collision energy of 15 V and scan time of 100 ms.The MRM ion pair for quantitative analysis was m/z→156.2/86.1.Results: The linear range of EDC was 0.03-2.25 μg·ml-1 (r=0.999 0).The limit of detection was 0.03 ng and the limit of quantitation was 0.08 ng.The average recovery was 98.3%(RSD=5.7%, n=9).Conclusion: The method is simple, rapid and accurate, and can be used for the quality control of EDC in ledipasvir.

Direct Acting Antiviral Agents in Korean Patients with Chronic Hepatitis C and Hemophilia Who Are Treatment-Naïve or Treatment-Experienced

BACKGROUND/AIMS: Chronic hepatitis C (CHC) is a major comorbidity in patients with hemophilia. METHODS: Patients (n=30) were enrolled between September 2015 and April 2016. Twenty-six patients were genotype 1 (1b, n=21; 1a, n=5) and four patients were genotype 2a/2b. Among 21 patients with genotype 1b, Y93H resistance-associated variants (RAVs) were detected in three patients (14.3%). We evaluated sustained virologic response (SVRs) at 12 weeks, as well as relapse and safety. RESULTS: Five patients with genotype 1a and three patients with genotype 1b (RAV positive) received ledipasvir/sofosbuvir for 12 weeks. SVR12 rate was 100% (8/8). Eleven patients with genotype 1b were treatment-naïve and received daclatasvir plus asunaprevir for 24 weeks. SVR12 rate was 91% (10/11). One patient experienced viral breakthrough without RAV at 12 weeks. Seven treatment-experienced patients with genotype 1b received daclatasvir plus asunaprevir for 24 weeks. SVR12 rate was 85.7% (6/7). One patient experienced viral breakthrough with RAV (L31M, Y93H) at 12 weeks. Four patients with genotype 2a/2b received sofosbuvir plus ribavirin for 12 weeks. SVR12 rate was 100% (4/4). No serious adverse event-related discontinuations were noted. CONCLUSIONS: New direct acting antiviral treatment achieved high SVRs rates at 12 weeks in CHC patients with hemophilia without serious adverse events.

Results of ledipasvir/sofosbuvir treatment on with HCV genotype 1b infection / Монголын Анагаах Ухаан

IntroductionGenotype 1 infection has been historically difficult to treat, but multiple recent studies have showntreatment results greater than high in these genotype 1b patients using well-tolerated, all-oral regimensconsisting of new direct-acting antiviral agents.GoalPurpose of the study was to define the effects of ledipasvir/sofosbuvir treatment on patients with HCVgenotype 1b infection.Materials and MethodsIn this study we enrolled 2 treatment-naive and 66 treatment-experienced, totally 68 patients who tookledipasvir/sofosbuvir during the period from January 2016 to March 2016. We used randomly selectedand double-blinded method in our clinical research. The descriptive and non-parametrical statisticaltests were conducted using SPSS Statistics 20.0.ResultsThe SVR12 and SVR24 rates were greater than 95% and no differences were observed in treatmentnaiveversus treatment-experienced patients.ConclusionTheSVR12 rates were found in 98.6% while the SVR24 was in 97.1% of 68 patients. Only 2.9% of thetotal cases were appeared relapse of HCV infection. These findings indicated needs of further studieson long-term effects of ledipasvir/sofosbuvir.