Résumé
Resumen Antecedentes: El tratamiento de la infección crónica por el virus de la hepatitis C (VHC) con antivirales de acción directa logra tasas de respuesta virológica sostenida superiores a 95 %. Sin embargo, el manejo del fracaso virológico sigue siendo un desafío clínico y la evidencia sobre el retratamiento es limitada, especialmente en poblaciones como los receptores de trasplante hepático (TH). Objetivo: Este estudio evaluó el régimen de sofosbuvir más glecaprevir/pibrentasvir (GLE/PIB) en receptores de TH en quienes falló el régimen basado en inhibidores de la proteína no estructural 5A (NS5A). Material y métodos: Estudio retrospectivo de 111 pacientes trasplantados entre enero de 2018 y diciembre de 2020; 18 pacientes presentaron infección recurrente por VHC posterior al TH, tres de ellos tuvieron antecedentes de al menos un régimen basado en inhibidores de NS5A. Se inició terapia de rescate con sofosbuvir más GLE/PIB durante 12 semanas posterior al TH; se registraron las características basales de los pacientes y sus desenlaces. Resultados: En los tres pacientes se logró obtener una carga viral indetectable de VHC a las 12 semanas de finalizar el tratamiento. No se observaron eventos adversos graves. Conclusión: En nuestra serie, sofosbuvir más GLE/PIB durante 12 semanas demostró ser una terapia de rescate efectiva y segura posterior al TH en pacientes previamente tratados con inhibidores de NS5A.
Abstract Background: Treatment of chronic hepatitis C virus (HCV) infection with direct-acting antivirals achieves a sustained virologic response rates higher than 95%. However, virologic failure remains a clinical challenge, and data on retreatment are limited, especially in special populations such as liver transplant (LT) recipients. Objective: This study evaluated the sofosbuvir plus glecaprevir-pibrentasvir (GLE/PIB) regimen in LT recipients who had failed to a nonstructural protein 5A (NS5A) inhibitor-based regimen. Material and methods: Retrospective study of 111 liver transplant recipients between January 2018 and December 2020; 18 patients presented with HCV recurrent infection after LT, out of whom three had a history of at least one NS5A inhibitor-based regimen. Salvage therapy with sofosbuvir plus GLE/PIB was started for 12 weeks; baseline characteristics and outcomes were recorded. Results: All three patients (100%) achieved an undetectable HCV viral load 12 weeks after treatment completion. No serious adverse events were observed. Conclusion: In our series, sofosbuvir plus GLE/PIB for 12 weeks is an effective and safe salvage therapy after LT in patients previously treated with NS5A inhibitors.
Résumé
Objective: Combination therapy with glecaprevir and pibrentasvir (G/P) has been shown to provide a sustained virologic response (SVR) rate of >97% in patients with chronic hepatitis C virus (HCV) infection in the first published real-world Japanese data. However, a recently published study showed that the treatment was often discontinued in patients ≥75 years old, resulting in low SVR in intention-to-treat (ITT) analysis. Thus, our aim was to evaluate real-world data for G/P therapy in patients ≥75 years of age, the population density of which is high in “rural” regions.Patients and Methods: We conducted a multicenter study to assess the efficacy and safety of G/P therapy for chronic HCV infection, in the North Kanto area in Japan.Results: Of the 308 patients enrolled, 294 (95.5%) completed the treatment according to the protocol. In ITT and per-protocol analyses, the overall SVR12 rate was 97.1% and 99.7%, respectively. The old-aged patients group consisted of 59 participants, 56 of whom (94.9%) completed the scheduled protocol. Although old-aged patients tended to have non-SVR factors such as liver cirrhosis, history of HCC, and prior DAA therapies, the SVR12 rates in old-aged patients were 98.3% and 100% in the ITT and PP analyses, respectively. Of 308 patients enrolled, adverse events were observed in 74 patients (24.0%), with grade ≥3 events in 8 patients (2.6%). There was no significant difference in any grade and grade ≥3 adverse events between the old-aged group and the rest of the study participants. Only one patient discontinued the treatment because of adverse events.Conclusion: G/P therapy is effective and safe for old-aged patients.
Résumé
OBJECTIVE：To evalua te the economics of glecaprevir/pibrentasvir （G/P）versus elbasvir/grazoprevir （EBR/GZR） in chronic hepatitis C genotype 1b（GT1b）treatment-naive patients without cirrhosis ，and to provide evidence support for medical and health decision-making. METHODS ：Under assuming the bid price of G/P and EBR/GZR therapy schemes before medical insurance negotiation was adopted （scenario 1）and assuming that the price of EBR/GZR was reduced by 85％ and the price of G/P was reduced by 80％（scenario 2），Markov model was developed to simulate the lifetime cost and health outcomes progress of 10 000 untreated chronic hepatitis C GT 1b treatment-naive patients without cirrhosis and calculate incremental cost-effectiveness ratio（ICER）. Single factor sensitivity analysis and probability sensitivity analysis were conducted to verify the results. The highest price（price reduction ratio ）of G/P scheme was analyzed with cost-effectiveness advantage ，when other parametes kept stable under scenario 2. RESULTS ：Under 2 kinds of scenarios ，compared with EBR/GZR scheme ，G/P scheme had higher cost （scenario 1：68 800 yuan vs. 62 338 yuan；scenario 2：13 760 yuan vs. 11 490 yuan）and healty utility （scenario 1：14.97 QALY vs. 14.90 QALY；scenario 2：14.97 QALY vs. 14.90 QALY），and ICER value of G/P was lower than willingness-to-pay threshold （scenario 1：92 314 yuan/QALY；scenario 2：32 428 yuan/QALY）. The change of most parameters in single factor sensitivity analysis didn ’t influence the results of base-case analysis ，and the findings from the base-case analysis were confirmed by probability sensitivity analyses. The price of G/P scheme needed to be reduced by at least 62％ to realize cost-effective advantage. CONCLUSIONS ： Under the set price scenario ，G/P scheme has cost-effectiveness advantages than EBR/GZR scheme in chronic hepatitis C GT 1b treatment-naive patients without cirrhosis.
Résumé
A novel, selective, precise, and sensitive stability indicating Reverse Phase-High Performance Liquid Chromatography(RP-HPLC) method has been developed and validated for simultaneous estimation of Glecaprevir (GLE) andPibrentasvir (PIB) for bulk and pharmaceutical dosage form. The chromatographic separation was accomplished ona Denali C18 column (150 mm × 4.6 mm, 5 µm) by using mobile phase buffer (pH 4.8) and acetonitrile in the ratio of60:40 v/v. An injection volume of 10 µl was used via manual rheodyne and the solute was detected at a UV wavelengthof 260 nm. The mobile phase was pumped at an ambient temperature of 30°C with a flow rate of 1 ml/minute. Theretention time of GLE and PIB were found to be 2.13 and 3.46 minutes, respectively. The Q2b validation of theproposed analytical method revealed several features; linear regression analysis data showed good linearity over theconcentration range 25–150 µg/ml for GLE and 10–60 µg/ml for PIB with r2 of 0.999 in both the cases and the meanrecovery of them were found to be 100.33% and 100.47%, respectively. The accuracy and precision aspects expressed<2% relative standard deviation value along with adequate robustness. The acid, alkali, neutral, dry heat, UV, andphoto-degradation studies demonstrated the formation of various degradation products. The proposed analyticalmethod proved to be suitable for the routine simultaneous analysis of both the drugs in bulk and tablet formulations.potential, morphology, encapsulation efficiency, and stability of microcapsules. The characterization results from eachformulation reported that the ratio of mangosteen peel extract and maltodextrin at level 50%:50% (MP3) producedmore proportional characteristics than other treatments. The formulation of mangosteen peel extract with maltodextrinat a balanced ratio could be used as an alternative supply and processing of functional food.