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Introducción: La infección por el virus C de la hepatitis resulta común en pacientes en hemodiálisis y se considera endémica en estas unidades. El tratamiento utilizado lo componían el interferón pegilado y la ribavirina, combinación que presentaba niveles de toxicidad y baja respuesta. Las drogas actuales aportan mejores resultados. Objetivos: Determinar la eficacia y seguridad de la terapia antiviral de acción directa para la infección del virus de la hepatitis C en pacientes con insuficiencia renal crónica en hemodiálisis. Métodos: Estudio descriptivo prospectivo en 19 pacientes en régimen de hemodiálisis y con infección por virus C, pertenecientes al Hospital General Docente "Dr. Mario Muñoz Monroy", desde diciembre de 2020 hasta septiembre de 2021," A todos se les prescribió durante 12 semanas Sofosbuvir® 400 mg más Daclatasvir® 60 mg diarios. Se caracterizaron las variables edad, sexo, fibrosis hepática por el índice aspartato-aminotransferasa/plaquetas, reacciones adversas y respuesta viral 12 semanas después del tratamiento. Resultados: La infección predominó en el grupo de 51 a 60 años (36,84 %). La mayoría de los pacientes mostró un índice aspartato-aminotransferasa/plaquetas ≤ 0,5, lo que correspondió con ausencia de fibrosis hepática significativa (14 pacientes). Una minoría de pacientes registró reacciones adversas. No se demostró toxicidad cardiovascular ni hepática. La totalidad de los pacientes manifestaron carga viral no detectable 12 semanas después del tratamiento. Conclusiones: La combinación de Sofosbuvir® con Daclatasvir® para el tratamiento de la infección por virus de la hepatitis C en pacientes con insuficiencia renal crónica en tratamiento de hemodiálisis resultó eficaz, bien tolerada y segura.
Introduction: Hepatitis C virus infection is common in hemodialysis patients and is considered endemic in these units. The treatment used consisted of pegylated interferon and ribavirin, a combination that presented levels of toxicity and low response. Current drugs bring better results. Objectives: To determine the efficacy and safety of direct-acting antiviral therapy for hepatitis C virus infection in patients with chronic renal failure on hemodialysis. Methods: Prospective descriptive study in 19 patients on hemodialysis and with virus C infection, belonging to "Dr. Mario Muñoz Monroy" Teaching General Hospital, from December 2020 to September 2021. All were prescribed for 12 weeks with Sofosbuvir® 400 mg plus Daclatasvir® 60 mg daily. The variables age, sex, liver fibrosis were characterized by the aspartate aminotransferase/platelet index, adverse reactions and viral response 12 weeks after treatment. Results: Infection predominated in the group of 51 to 60 years (36.84%). Most patients showed an aspartate aminotransferase/platelet ratio ≤ 0.5, corresponding to the absence of significant liver fibrosis (14 patients). A minority of patients reported adverse reactions. No cardiovascular or hepatic toxicity was demonstrated. All patients had an undetectable viral load 12 weeks after treatment. Conclusions: The combination of Sofosbuvir® with Daclatasvir® for the treatment of hepatitis C virus infection in patients with chronic renal failure undergoing hemodialysis was effective, well tolerated and safe.
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Background: Assessment of efficacy and safety of daclatasvir+sofosbuvir+ribavirin (DCV+SOF+RBV) for 12 weeks as compare to daclatasvir and sofusbuvirfor 24 weeks in decompensated cirrhotic patients due to hepatitis C virus (HCV) genotype 3 infection. Methods: An observational, prospective, COHORTstudy over 1 year, in decompensated cirrhosis due to G3-HCV infected adult patients. Treatment was a combination of sofosbuvir 400 mg/day+daclatasvir 60 mg/day, with or without a weight-adjusted dosing of ribavirin for 12 or 24 weeks. The primary efficacyendpoint was sustained virologic response rates 12 weeks after therapy (SVR 12). The primary safety endpoint was treatment withdrawal rates secondary to severe adverse events. Results: The32 patients were screened and 2 were excluded, one patient due toassociated HBV+, one patient due to severe anemia. 30 patients were randomized. All 30 randomized patients were divided into two groups. Group 1 was given SOF+DCV+RBV for 12 weeks while group 2 patients were given SOF+DCV for 24 weeks. 81.8% of the participants in the group1 achieved SVR 12. The 90.9% of the participants in the group 2 achieved SVR12 (p=1). No other patient or treatment basal variables influenced the treatment effectiveness. No patient treatment withdrawal secondary to severe adverse events was observed. Conclusions: Both the regimen SOF+DCV with or without RBV are highly efficacious and safe. Addition of RBV can reduce the treatment duration to 12 weeks, and it will further improve compliance and more convenient for the patients.
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RESUMO Os medicamentos reaproveitados são importantes em contextos de recursos limitados porque as intervenções estão mais rapidamente disponíveis, já foram testadas com segurança em outras populações e são, em geral, mais baratas. Os medicamentos reaproveitados são uma solução eficaz, especialmente para doenças emergentes, como a COVID-19. O estudo REVOLUTIOn visa avaliar três medicamentos antivirais reaproveitados: atazanavir, daclatasvir e sofosbuvir, já utilizados em pacientes infectados pelo HIV ou pelo vírus da hepatite C, em um estudo randomizado, controlado por placebo, adaptativo, multibraço e em múltiplos estágios. Os medicamentos serão testados simultaneamente em um ensaio de Fase II para primeiro identificar se algum deles, isoladamente ou em combinação, reduz a carga viral. Se reduzirem, será iniciado um estudo de Fase III para investigar se tais medicamentos são capazes de aumentar o número de dias sem suporte respiratório. Os participantes devem ser adultos hospitalizados com idade ≥ 18 anos com início dos sintomas ≤ 9 dias e saturação de oxigênio ≤ 94% em ar ambiente ou necessidade de oxigênio suplementar para manter saturação de oxigênio > 94%. O tamanho total esperado da amostra varia entre 252 e 1.005 participantes, dependendo do número de estágios que serão concluídos no estudo. Assim, o protocolo é aqui descrito em detalhes, juntamente do plano de análise estatística. Em conclusão, o estudo REVOLUTIOn foi concebido para fornecer evidências se o atazanavir, o daclatasvir ou o sofosbuvir reduzem a carga viral de SARS-CoV-2 em pacientes com COVID-19 e aumentam o número de dias em que os pacientes ficam sem suporte respiratório. Neste artigo de protocolo, descrevem-se a fundamentação, o desenho e a situação do ensaio. Identificador do ClinicalTrials.gov:NCT04468087
ABSTRACT Repurposed drugs are important in resource-limited settings because the interventions are more rapidly available, have already been tested safely in other populations and are inexpensive. Repurposed drugs are an effective solution, especially for emerging diseases such as COVID-19. The REVOLUTIOn trial has the objective of evaluating three repurposed antiviral drugs, atazanavir, daclatasvir and sofosbuvir, already used for HIV- and hepatitis C virus-infected patients in a randomized, placebo-controlled, adaptive, multiarm, multistage study. The drugs will be tested simultaneously in a Phase II trial to first identify whether any of these drugs alone or in combination reduce the viral load. If they do, a Phase III trial will be initiated to investigate if these medications are capable of increasing the number of days free respiratory support. Participants must be hospitalized adults aged ≥ 18 years with initiation of symptoms ≤ 9 days and SpO2 ≤ 94% in room air or a need for supplemental oxygen to maintain an SpO2 > 94%. The expected total sample size ranges from 252 to 1,005 participants, depending on the number of stages that will be completed in the study. Hence, the protocol is described here in detail together with the statistical analysis plan. In conclusion, the REVOLUTIOn trial is designed to provide evidence on whether atazanavir, daclatasvir or sofosbuvir decrease the SARS-CoV-2 load in patients with COVID-19 and increase the number of days patients are free of respiratory support. In this protocol paper, we describe the rationale, design, and status of the trial. ClinicalTrials.gov identifier:NCT04468087
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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).
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Humans , Treatment Outcome , Hepatitis C, Chronic , Patients , Case-Control Studies , SofosbuvirABSTRACT
ABSTRACT Despite the high sustained virologic response (SVR) rates of direct-acting antiviral (DAAs) therapy, a small number of patients does not eradicate the virus, and these patients represent a challenge. This study aims to compare the outcomes of three second-line regimens for DAAs-experienced patients with chronic hepatitis C (CHC). This prospective observational study was conducted at the Damanhur Viral Hepatitis Center from January 2017 to February 2020. We included patients with CHC who did not achieve SVR after the complete course of Sofosbuvir/Daclatasvir±Ribavirin (SOF/DAC±RBV). The primary endpoint was SVR-12 after re-treatment. This study included 360 patients (with a mean age of 51.53±11.38 years). Approximately 51.1% of the patients were males, and 65.5% had liver cirrhosis. All patients of group 1 (45 patients) received SOF/VEL/VOX over 12-weeks; SVR-12 was achieved in 44 patients (97.8%). Group 2 (28 patients) received SOF/DAC/RBV over 24-weeks; (one patient was lost during follow-ups and one patient discontinued treatment due to hepatic decompensation). SVR-12 was achieved in 25 patients (96.2%). Group 3 (287 patients) received SOF/Ombitasvir/Paritaprevir/Ritonavir/RBV) over 12-weeks. Eight patients were lost during follow-ups, and one patient discontinued treatment due to grade 4 adverse events. SVR-12 was achieved in 276 patients (99.3%). There was no difference between the groups regarding their age, gender distribution, baseline viral load or comorbidities. Adverse events (thrombocytopenia, anemia, hyperbilirubinaemia and prolonged INR) were significantly higher in group 3, while group 1 did not experience any. The three studied retreatment regimens can be used for DAAs treatment-experienced patients considering availability. The SOF/VEL/VOX combination had the least adverse events.
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ABSTRACT Background: To analyze the effectiveness and the safety of Sofosbuvir-based regimens to treat patients with chronic hepatitis C virus (HCV) infection and chronic kidney disease (CKD). Methods: A retrospective, observational study in patients with chronic HCV infection and CKD treated with Sofosbuvir-based regimens was performed. Liver fibrosis, comorbidities, HCV genotype and sustained virological resposnse (SVR) at 12th week post-treatment were evaluated. Kidney function was accessed by serum creatinine and glomerular filtration rate (GFR). The assumed level of significance was 5 %. Results: Thirty-five patients were treated. The mean age was 52.1 ± 10.9 years, 19 (54.3 %) were women, 32 (91.4 %) were already kidney transplanted and 3 (8.6 %) were on hemodialysis. The SVR by intention to treat was 88.6 %. The mean GFR was 65.8 ± 28.6 and 63.7 ± 28.3 ml/min pre- and post-treatment respectively (p > 0.05). Treatment was interrupted in 1 (2.85 %) patient due to anemia and in 2 (5.7 %) due to loss of kidney function. Conclusion: Sofosbuvir-based regimens are effective to treat HCV in patients with CKD. In patients with mild CKD this type of therapy seems to be safe.
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Humans , Male , Female , Adult , Middle Aged , Aged , Antiviral Agents/therapeutic use , Hepatitis C, Chronic/drug therapy , Renal Insufficiency, Chronic/physiopathology , Sofosbuvir/therapeutic use , Severity of Illness Index , Reproducibility of Results , Retrospective Studies , Analysis of Variance , Kidney Transplantation , Treatment Outcome , Statistics, Nonparametric , Creatinine/blood , Renal Insufficiency, Chronic/therapy , Sustained Virologic Response , Glomerular Filtration Rate , Imidazoles/therapeutic use , Immunosuppressive Agents/therapeutic useABSTRACT
Interferon-free direct-acting antiviral agent (DAA) therapy is preferred for the treatment of chronic hepatitis C (CHC) patients as it exhibits a higher rate of sustained virologic response (SVR), along with reduction in treatment related adverse drug reactions (ADR), which elevates the quality of life (QOL) of patients. The study aims to evaluate the healthrelated quality of life (HRQOL) in patients with CHC, receiving Daclatasvir or velpatasvir (DCV/VEL) therapy, using Short Form-36 (SF-36) as a tool. Methods: The study involves 50 CHC patients receiving DCV/VEL, who’s HRQOL was measured using SF-36. Laboratory investigational data and SVR was recorded, and SF-36 was filled by the patient at baseline (prior to therapy), week 12 (post initiation of therapy), end of treatment (EOT), and week 24 (post initiation of therapy. HRQOL were analyzed at week 24. The association between laboratory data and HRQOL was also evaluated. Results: In regard to HRQOL, statistically significant changes were observed in physical functioning, general health, and emotional role functioning in the period between baseline to week 12 and week 24, respectively. A considerable change was observed in laboratory parameters such as aminotranferases, platelet count, and Fibrosis-4 (Fib-4) index at each time point of study as compared to baseline. Conclusion: It was found that HRQOL of patients with CHC improved significantly along with hepatic functions during the clinical course of interferon-free DAA therapy (DCV/VEL).
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Recurrent hepatitis C (HCV) after liver transplantation (LT) is an important cause of morbidity and mortality. Antiviral treatment is recommended to avoid unfavorable outcomes. Direct-acting antivirals (DAA) have transformed HCV treatment, with higher efficacy and fewer side-effects than interferon-based therapies traditionally used. To evaluate DAA treatment outcomes at a Brazilian transplant unit, data of patients who finished HCV treatment at the Liver Transplant Unit of the University of Campinas were analyzed. Treatment consisted of sofosbuvir, daclatasvir, and ribavirin, for 12 or 24 weeks, according to the national guidelines. Fifty-five patients completed antiviral treatment and 54 had HCV-viral load results available. The majority of patients were male (78%), 58 years old on average, 65% had hepatocellular carcinoma (HCC) before LT, and 67% were interferon treatment-experienced. Most patients had HCV genotype 1 (65%), 35% had genotype 3, and started treatment on an average of 38 months after LT (range: 2-228). Fifty-eight percent were treated for 12 weeks and 42% for 24 weeks, using a mean dose of ribavirin of 10.1 mg/kg (4.2-16.1). There were no treatment interruptions due to serious side effects. The sustained virological response rate was 98%. Only one patient relapsed, a genotype 3 cirrhotic treated for 12 weeks. The average follow-up after starting antivirals was 20 months. There were no recurrences of HCC, but there was one rejection episode and one cirrhosis decompensation episode, both 12 weeks after treatment. DAA treatment is safe and effective in the post-LT setting and was not associated to HCC recurrence in the cohort studied.
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Humans , Male , Female , Adult , Middle Aged , Aged , Antiviral Agents/administration & dosage , Ribavirin/administration & dosage , Liver Transplantation/adverse effects , Hepatitis C/drug therapy , Sofosbuvir/administration & dosage , Imidazoles/administration & dosage , Recurrence , Retrospective Studies , Treatment Outcome , Viral Load , Drug Therapy, Combination , Sustained Virologic Response , GenotypeABSTRACT
Objective To evaluate the clinical efficacy and safety of ritonavir-boosted danoprevir (DNVr) combined with daclatasvir (DCV) in the treatment of patients with genotype 1b chronic hepatitis C (CHC).Methods Thirty-three patients with genotype 1b CHC admitted in the Department of Infectious Diseases of the First Affiliated Hospital of Nanchang University from August 2018 to February 2019 were enrolled.All the patients received DNVr +DCV antiviral treatment.HCV RNA levels were detected before and 2, 4, 12 weeks after treatment, and after drug withdrawal , respectively.Indicators of liver and kidney function and adverse events were observed.ANOVAV of repeated measurement was used to analyze the data. Results The baseline viral loads of 33 patients ranged from 1.12×104 to 1.76×107 IU／mL.Two weeks after treatment the viral loads of all patients were down to the lowest limit of detection (＜500 IU／mL). Serum ALT, AST and TBil levels returned to norml ( F＝58.26, 14.49 and 20.16, all P＜0.05) and sustained virologic response reached 100%12 weeks after drug withdrawal.Three cases had minor adverse reactions during the treatment.Conclusion DNVr combined with DCV can achieve a rapid and strong virological response in the treatment of patients with genotype 1b CHC with good safety.
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BACKGROUND: The long-term data with direct acting antiviral agents were rare. This study investigated the durability of a sustained virologic response (SVR) and the improvement of fibrosis after daclatasvir and asunaprevir (DCV/ASV) treatment in genotype 1b (GT1b) hepatitis C virus (HCV)-infected patients. METHODS: A total of 288 HCV GT1b patients without baseline non-structural 5A (NS5A) resistance-associated substitution (RAS) treated with DCV/ASV were enrolled. Virologic response was measured at 12 weeks and 1 year after treatment completion. In cirrhotic patients, liver function, aspartate transaminase to platelet ratio index (APRI), FIB-4 index, fibrosis index (FI), and liver stiffness measurement (LSM) at baseline and 1 year after treatment completion were evaluated. RESULTS: SVR12 was obtained in 278 patients (96.5%). Six patients who checked NS5A RAS after treatment failure were RAS positive. Only one patient showed no durability of SVR. In cirrhotic patients who achieved SVR12 (n = 59), the changes of albumin (3.8 [2.2–4.7] to 4.3 [2.4–4.9] g/dL; P < 0.001), platelet count (99 [40–329] to 118 [40–399] × 103/mm3; P < 0.001), APRI (1.8 [0.1–14.8] to 0.6 [0.1–4.8]; P < 0.001), FIB-4 index (5.45 [0.6–32.8] to 3.3 [0.4–12.2]; P < 0.001), FI (5.5 [0.6–32.8] to 3.3 [0.4–12.2]; P < 0.001), and LSM (17.2 [5.3–48.0] to 11.2 [3.7–28.1] kPa; P = 0.001) between baseline and 1 year after treatment completion were observed. CONCLUSION: DCV/ASV treatment for HCV GT1b infected patients without RAS achieved high SVR rates and showed durable SVR. Cirrhotic patients who achieved SVR12 showed the improvement of liver function and fibrosis markers.
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Humans , Antiviral Agents , Aspartate Aminotransferases , Blood Platelets , Fibrosis , Genotype , Hepacivirus , Hepatitis C , Hepatitis , Liver , Platelet Count , Treatment FailureABSTRACT
BACKGROUND/AIMS: We evaluated the efficacy and safety of daclatasvir (DCV) and asunaprevir (ASV) in patients with chronic hepatitis C virus (HCV) infection on hemodialysis. METHODS: We performed a single-arm, multicenter prospective study. Twenty-one chronic hemodialysis patients with HCV infection were prospectively enrolled from February 2016 to April 2017. We evaluated the virological responses at weeks 4, 12, and 24 (end of treatment [EOT]) and the sustained virological response at 12 weeks after the EOT (SVR12). The tolerability and safety of the drugs were also assessed. RESULTS: None of the 20 patients had the NS5A resistance-associated variant (NS5A RAV), and one patient was indeterminate for the NS5A RAV. Seventeen patients (80%) completed the 24 weeks of treatment with DCV and ASV. Four patients discontinued the study prior to week 12. In an intention-to-treat analysis, the SVR12 was 76.1%. In a per-protocol analysis, patients who completed DCV and ASV treatment achieved an SVR12 of 100%. DCV and ASV were well tolerated by the majority of patients. Three patients discontinued treatment due to adverse events (AEs) including dizziness, dyspnea, and neutropenia. The patient with indeterminate NS5A RAV showed viral breakthrough and discontinued treatment. CONCLUSIONS: DCV and ASV combination therapy in chronic hemodialysis patients with HCV infection achieved a high SVR12 rate with few AEs. To maximize the SVR12 rate, it is important to identify candidates by baseline RAV testing. Close monitoring of the safety and tolerability of DCV and ASV may be necessary in HCV-infected patients on hemodialysis. (ClinicalTrials.gov ID NCT02580474)
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Humans , Dizziness , Dyspnea , Hepacivirus , Hepatitis C , Hepatitis C, Chronic , Hepatitis , Neutropenia , Prospective Studies , Renal DialysisABSTRACT
Objective@#To study the efficacy and safety of sofosbuvir and daclatasvir regimens for patients who received kidney transplantation (KT) with hepatitis C virus (HCV) infection.@*Methods@#This study enrolled a prospective cohort of consecutive KT patients with HCV infection from March 2016 to January 2018 in the hepatology Department of the Second Hospital of Shandong University. They were given sofosbuvir combined with daclatasvir, with or without ribavirin. The course of treatment was 12 weeks or 24 weeks. Clinical assessment, conventional liver and kidney biochemical parameters, hemoglobin, serum HCV RNA, as well as the types of immunosuppressive drugs and their doses were assessed routinely as follows: at the beginning of treatment; 2, 4, and 8 wk post treatment; at the end of treatment (EOT); and at 12, 24 wk after the therapy was completed. Adverse events and adjustment of anti-rejection drugs were surveilled during the treatment period.@*Results@#A total of 13 patients were enrolled. All patients were naive to treatment. Their mean age was 46.84±7.79 years. There were 10 males and 3 females, 3 patients had cirrhosis (1 cases had decompensated cirrhosis), 10 patients had no cirrhosis. They were infected with HCV genotype 1 (6/13 GT1b), genotype 3 (2/13 GT3a) and genotype 6 (3/13 GT6a), and genotype 2 (2/13 GT2a). Twelve patients′ estimated glomerular filtration rate (eGFR) was > 30 ml/min per 1.73 m2 at the beginning of treatment, 1 patient′s eGFR was <30 ml/min·1.73 m2; 9 patients received 12 wk therapy, 4 patients received 24 wk therapy. Twelve patients had undetectable viral load by week 4 of treatment. All patients had undetectable HCV viral load at the end of treatment. Sustained virological response (SVR) 12 rate was achieved in 100% (13/13) of the recipients. The basic renal function remained stable during the course of treatment. No serious adverse events were observed during the treatment. Antiviral therapy was not discontinued due to side effects in any patient.@*Conclusions@#Sofosbuvir and daclatasvir for treatment of KT patients with HCV infection are highly effective and safe.
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Objective To investigate the efficacy and safety of daclatavir combined with sofosbuvir treatment in chronic hepatitis C (CHC) in the real world.Methods A total of 56 CHC patients administrated with daclatavir (60 mg/d) combined with sofosbuvir (400 mg/d) in Huzhou Central Hospital from February to June in 2018 were enrolled.All patients were administrated with daclatavir combined with sofosbuvir for 12 weeks and followed up for 24 weeks.The virological response and the effect of antiviral therapy on hepatic fibrosis were analyzed.Non-structural protein 5A (NS5A) region mutation sequence was detected by Sanger method.Safety and the adverse events were observed.The t test,chi-square test and Mann-Whitney U test were used to analyze the data.Results Hepatitis C virus (HCV) RNA of all patients treated with daclatavir and sofosbuvir was undectable after eight-week treatment.Sustained virological response at 12 weeks post-treatment (SVR12) was 98.1％ (52/53).Gender,globulin,insulin,triglyceride and hemoglobin were correlated with virus clearance (x2 =4.47,t=2.51,U=1.98,U=2.32 and t =2.03,respectively,all P＜0.05).At 12 weeks of the end of the treatment,serum procollagen type Ⅲ,collagen type Ⅳ,liver stiffness measurement (LSM) value,aspartate aminotransferase-to-platelet ratio Index (APRI) score and fibrosis index based on the four factors (FIB-4) score were all improved (U =2.03,2.15,2.19,2.12 and 2.26,respectively,all P ＜ 0.05).At 24 weeks of the end of treatment,these indexes showed clear improvement (U =2.09,2.28,2.24,2.33 and 2.46,respectively,all P ＜ 0.05).Eight patients had Y93H or L31M resistance-related substitution mutations.Two out of eight patients with variants had negative coversion of HCV RNA and 44.4％ (20/45) showed no variants after two weeks of treatment.There was no significant difference (x2 =1.11,P ＞ 0.05).During the treatment,patients developed dizziness,fatigue,nausea and vomiting,panic,insomnia,sleepiness and sexual function enhancement.Conclusion Daclatavir in combination with sophobuvir shows high virological response and good safety in the treatment of chronic hepatitis C,and liver fibrosis is improved after clearance of HCV.
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Objective@#To investigate the efficacy and safety of daclatavir combined with sofosbuvir treatment in chronic hepatitis C (CHC) in the real world.@*Methods@#A total of 56 CHC patients administrated with daclatavir (60 mg/d) combined with sofosbuvir (400 mg/d) in Huzhou Central Hospital from February to June in 2018 were enrolled. All patients were administrated with daclatavir combined with sofosbuvir for 12 weeks and followed up for 24 weeks. The virological response and the effect of antiviral therapy on hepatic fibrosis were analyzed. Non-structural protein 5A (NS5A) region mutation sequence was detected by Sanger method. Safety and the adverse events were observed. The t test, chi-square test and Mann-Whitney U test were used to analyze the data.@*Results@#Hepatitis C virus (HCV) RNA of all patients treated with daclatavir and sofosbuvir was undectable after eight-week treatment. Sustained virological response at 12 weeks post-treatment (SVR12) was 98.1% (52/53). Gender, globulin, insulin, triglyceride and hemoglobin were correlated with virus clearance (χ2= 4.47, t=2.51, U=1.98, U=2.32 and t=2.03, respectively, all P<0.05). At 12 weeks of the end of the treatment, serum procollagen type Ⅲ, collagen type Ⅳ, liver stiffness measurement (LSM) value, aspartate aminotransferase-to-platelet ratio Index (APRI) score and fibrosis index based on the four factors (FIB-4) score were all improved (U=2.03, 2.15, 2.19, 2.12 and 2.26, respectively, all P<0.05). At 24 weeks of the end of treatment, these indexes showed clear improvement (U=2.09, 2.28, 2.24, 2.33 and 2.46, respectively, all P<0.05). Eight patients had Y93H or L31M resistance-related substitution mutations. Two out of eight patients with variants had negative coversion of HCV RNA and 44.4% (20/45) showed no variants after two weeks of treatment. There was no significant difference (χ2 = 1.11, P > 0.05). During the treatment, patients developed dizziness, fatigue, nausea and vomiting, panic, insomnia, sleepiness and sexual function enhancement.@*Conclusion@#Daclatavir in combination with sophobuvir shows high virological response and good safety in the treatment of chronic hepatitis C, and liver fibrosis is improved after clearance of HCV.
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ABSTRACT Introduction Chronic hepatitis C virus infection is one of the major causes of cirrhosis, hepatocellular carcinoma and liver transplantation. Treatment using direct-acting antivirals has revolutionized the treatment of hepatitis C virus, increasing long-term prognosis after cure. The goal of the present study was to evaluate the effectiveness of direct-acting antivirals in a Public Health System in southern Brazil. Methods A retrospective study evaluated all patients with chronic hepatitis C virus infection who underwent treatment at one center of the Public Health Department of the State of Rio Grande do Sul - Brazil, according to the Brazilian Clinical Protocol and Therapeutic Guidelines. The effectiveness was assessed in terms sustained virological response 12 weeks after the end of treatment. Results A total of 1002 patients who were treated for chronic hepatitis C virus infection were evaluated. The mean age was 58.6 years, 557 patients (55.6%) were male and 550 (54.9%) were cirrhotic. Overall sustained virological response was observed in 936 (93.4%) patients. There was a difference in sustained virological response rate varied according to sex, 91.6% in men and 95.7% in women (p= 0.009), length of treatment in genotype 1, 92.7% with 12 weeks and 99.1 with 24 weeks (p= 0.040), and genotype, 94.7% in genotype 1, 91.7% in genotype 2, and 91.4% in genotype 3 (p= 0.047). Conclusion The treatment of chronic hepatitis C virus infection for genotypes 1, 2 or 3 with the therapeutic regimens established by the Brazilian guidelines showed high rates of SVR, even in cirrhotic patients.
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Humans , Male , Female , Adult , Middle Aged , Aged , Antiviral Agents/therapeutic use , Public Health/statistics & numerical data , Hepatitis C, Chronic/drug therapy , Sustained Virologic Response , Ribavirin/therapeutic use , Brazil , Retrospective Studies , Practice Guidelines as Topic , Hepacivirus/genetics , Viral Load , Hepatitis C, Chronic/genetics , Drug Therapy, Combination , Simeprevir/therapeutic use , Sofosbuvir/therapeutic use , Genotype , Imidazoles/therapeutic use , Liver CirrhosisABSTRACT
Context: Patients with thalassaemia are at risk of infections such as hepatitis C virus (HCV) due to their repeated blood transfusions; meanwhile, the treatment of thalassaemia patients who had developed HCV infection is a controversial issue. Aims: Although the effectiveness of direct-acting antivirals on HCV infection has been confirmed, their side-effects as well as effects on haematological factors due to the resultant need for blood transfusion remain to be further understood. Materials and Methods: In this study, 61 patients with major beta thalassaemia and HCV infection, and who had a history of interferon treatment failure were examined. The patients underwent a 24-week treatment with sofosbuvir (SOF) and daclatasvir (DAC). Sustained virological response 12 was used to assess response to treatment. At the end of the study, the need for blood transfusion and serum ferritin was evaluated. Results: About 98.4% of the patients responded to the treatment, and only one patient with genotype 1b did not respond positively. No significant complications necessitating treatment cessation were observed, and all the patients tolerated the treatment well. The level of liver enzymes showed a significant reduction 12 weeks after the treatment. The need for blood transfusions in patients before treatment was averagely 1.595 ± 0.65 bag per month, in which 1.593 ± 0.64 bags were received after treatment (P = 0.9). This regimen did not affect the amount of anaemia in patients and did not differentiate the need for blood transfusions. The rate of haemoglobin before treatment was 9.5 ± 1.42 g/dl, which reached 9.6 ± 1.6 g/dl after treatment (P = 0.54). Ferritin levels decreased significantly (from 1948.08 ± 1539.54 to 1315.73 ± 1207.67 ng/ml) (P = 0.001) in the patients after the treatment. Conclusion: Combination of SOF and DAC is an effective and tolerable treatment regimen without affect on the amount of anaemia in patients and did not differentiate the need for blood transfusions.
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Objective To explore the efficacy and safety of daclatasvir (DCV ) combined with asunprevir (ASV) for chronic genotype 1b (GT1b) hepatitis C .Methods Twenty-nine GT1b hepatitis C patients who were treated with DCV combined ASV in Henan Provincial People′s Hospital from September 2017 to November 2017 were included .Hepatitis C virus (HCV ) RNA levels were tested before treatment ,1 week ,2 weeks ,3 weeks ,4 weeks ,8 weeks ,12 weeks and 24 weeks after treatment , and 12 weeks after the end of the treatment .The comorbidities ,combined use of drugs and adverse clinical events were registered .T test was used to compare the measurement data with normal distribution and M (P25,P75) was used for measurement data with non-normal distribution .Results A total of 29 patients with GT1b were included ,with 4 cirrhosis cases and 25 non cirrhotic cases .Seven patients had history of previous interferon and ribavirin combination treatment .There were 9 patients with comorbidity and 7 patients with combined medication . Finally , 25 patients completed a 24-week course of antiviral treatment ;3 patients were lost to follow-up ,and 1 patient withdrew after 16weeks of antiviral treatment because of a virus rebound .Of the 26 followed up patients ,25 achieved sustained virological response at 12-week (SVR12 ) , and one patient failed .And the HCV RNA NS5A resistance-associated variants (RAV) were detected in the patients with treatment failure .No severe adverse clinical events occurred in 26 patients .Conclusions DCV combined with ASV is effective and safe in the treatment of GT 1b chronic hepatitis C .However , the effect of RAV on therapeutic efficacy should be concerned during the treatment .
ABSTRACT
BACKGROUND/AIMS: Although daclatasvir with asunaprevir was approved in Japan for interferon ineligible or intolerant patients, patients aged ≥75 years were excluded in the phase III trial. The present study aimed to evaluate the safety and efficacy of this therapy for elderly patients aged ≥75 years and to clarify whether an extremely high sustained virological response (SVR) rate can be achieved, even in a real-world setting when patients with resistance-associated substitutions (RASs) to nonstructural protein 5A (NS5A) inhibitors or prior simeprevir failure are excluded. METHODS: Daclatasvir (60 mg) and asunaprevir (100 mg) were orally administered daily for 24 weeks. Patients without pre-existing NS5A RASs and simeprevir failure were enrolled in this study. RESULTS: Overall, 110 patients were treated. The median age was 73 years old. The SVR rates of total patients, those aged ≥75 years, and those aged < 75 years were 97% (107/110), 98% (46/47), and 97% (61/63), respectively. The treatment of two patients (2%) was discontinued because of adverse events. CONCLUSIONS: Daclatasvir with asunaprevir was a safe treatment, even in patients aged ≥75 years. When patients without pre-existing NS5A RASs and prior simeprevir failure were selected, an extremely high SVR rate could be achieved irrespective of age.
Subject(s)
Aged , Humans , Hepacivirus , Interferons , Japan , SimeprevirABSTRACT
Objective@#To evaluate the efficacy and safety of DCV-based DAAs therapy for chronic HCV infected Chinese patients.@*Methods@#An open-label, non-randomized, prospective study was designed. Fifty-two patients with chronic HCV infection were enrolled. Among them, there was one patient after liver transplantation, 2 patients after kidney transplantation, 3 patients with hepatocellular carcinoma, and 4 patients with HBV infection. Thirteen cases with chronic hepatitis C (one compensated cirrhosis) who were negative for resistance-related variants [NS5A RAS (-)] of gene 1b and NS5A were treated with daclatasvir (DCV) + asunaprevir (ASV) for 24 weeks. Twenty-five cases of CHC (six compensated cirrhosis) with GT 1b, 2a, 3a, 3b, 6a were treated with DCV + SOF ± RBV for 24 weeks. 8 cases with decompensated cirrhosis of gene 1b and NS5A RAS(-) were given DCV + SOF + RBV regimen for 12 weeks. Six cases with decompensated cirrhosis, of gene 2a, 1b, 2a, 3a, 3b, were given DCV + SOF + RBV regimen for 24 weeks. HCV RNA, blood routine test, liver and kidney function, and upper abdominal ultrasound/MRI were measured at baseline, 4 weeks of treatment, end of treatment, and 12 weeks of follow-up. The incidence of adverse events and laboratory abnormalities during treatment were recorded. A t-test was used to compare the measurement data between two groups, and analysis of variance was used to compare the measurement data between multiple groups.@*Results@#Sixteen patients (100%) achieved SVR12 after treatment, with 0% recurrence rate. Rapid virological response (RVR) of the four treatment regimens were 76.92%, 54.17%, 87.50%, and 83.33%, respectively, and 32 patients achieved 100% virological response after the completion of treatment. The incidence of adverse events of chronic hepatitis C with cirrhosis and decompensated cirrhosis was 62.5% and 64.29%, respectively. The most common adverse event was fatigue in CHC (25.00%), and elevated indirect bilirubin in decompensated cirrhosis (42.86%). No serious adverse drug events, deaths or adverse reactions occurred.@*Conclusion@#DCV-based DAAs regimen is promising option for the treatment of HCV genotypes, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, and HCV infection after liver/kidney transplantation in china. Above all, it has high SVR12 with good tolerability and safety profile.
ABSTRACT
All-oral, pan-genotypic combination of direct-acting antiviral agents is currently clinically prescribed trends in the management of chronic hepatitis C virus infection. The combination of daclatasvir and sofosbuvir has proven strong antiviral activity across all common genotypes in clinical trials and real world studies. Furthermore, it can be safely used in patients with advanced liver disease, HCV/HIV co-infection, or HCV recurrence after liver transplantation, more patients will gain clinical benefits. We aim to summarize the clinical progress about this combination.