scholarly journals Ribavirin at the Era of Novel Direct Antiviral Agents for the Treatment of Hepatitis C Virus Infection: Relevance of Pharmacological Monitoring

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Pierre Pradat ◽  
Victor Virlogeux ◽  
Marie-Claude Gagnieu ◽  
Fabien Zoulim ◽  
François Bailly
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virological Response ◽  
Antiviral Agents ◽  
Area Under The Curve ◽  
Direct Acting Antiviral ◽  
Dose Adaptation ◽  
Virological Relapse ◽  
Direct Acting

Ribavirin is often used for the treatment of hepatitis C virus (HCV) infection. Although its mechanisms of action remain to be clearly elucidated, ribavirin plays a beneficial role for achieving virological response and decreasing the rate of virological relapse after treatment cessation. However, ribavirin may induce side effects leading to early treatment discontinuation. Among them, hemolytic anemia is the most frequent and results from intraerythrocyte accumulation. Pharmacological studies have shown that early ribavirin exposure assessed by the area under the curve (AUC) at day 0 and ribavirin trough concentration during the first three months of therapy were correlated with sustained virological response (SVR). These studies highlighted the relevance of ribavirin pharmacologic monitoring and early dose adaptation during therapy. Although the role of ribavirin within new direct acting antiviral (DAA) combinations will probably decrease in the future, its potential benefit in difficult-to-treat patients such as patients with severe hepatopathy or patients who failed triple therapy including patients with multiresistance will need to be further investigated.

scholarly journals Efficacy and Safety of Sofosbuvir-Based Direct-Acting Antiviral Agents Treatment for Patients with Genotype 3/6 Hepatitis C Virus Infection

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yong-yu Mei ◽  
You-ming Chen ◽  
Yuan-kai Wu ◽  
Xiao-hong Zhang ◽  
Wen-xiong Xu
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virological Response ◽  
Antiviral Agents ◽  
Hcv Infection ◽  
Efficacy And Safety ◽  
Direct Acting Antiviral ◽  
Direct Acting ◽  
Direct Acting Antiviral Agents

Aims. The aim is to evaluate the efficacy and safety of Sofosbuvir- (SOF-) based direct-acting antiviral agents (DAAs) treatment for patients with genotype (GT) 3/6 hepatitis C virus (HCV) infection. Methods. Patients infected with GT 3/6 HCV and treated with SOF-based DAAs were enrolled in this prospective, open, single-center, and real-world study. Drugs included Sofosbuvir (SOF), Velpatasvir (VEL), Daclatasvir (DCV), and Ribavirin (RBV). The treatment regimens included SOF + RBV for 24 weeks, SOF + DCV ± RBV for 12/24 weeks, and SOF/VEL ± RBV for 12 weeks. Results. A total of 54 patients were included. Age was 42.5 ± 10.4 years. Baseline HCV RNA was 6.29 ± 0.89log10 IU/mL. The numbers of GT 3a, 3b, and 6a patients were 10, 12, and 32, respectively. The numbers of chronic hepatitis, compensated cirrhosis, and decompensated cirrhosis patients were 39, 9, and 6, respectively. In patients with chronic hepatitis C and liver cirrhosis, sustained virological response 12 weeks after the end of treatment (SVR12) was 97.4% and 96.7%, respectively, and rapid virological response (RVR) was 75.0% and 57.1%, respectively. SVR12 of GT3a, GT3b, and GT6a was 100%, 83.3%, and 97%, respectively. ALT normality rate in chronic hepatitis group is higher than that in cirrhosis group at 4 weeks of treatment (89.7% versus 60.0%, p  = 0.033) and at 12 weeks after EOT (94.9% versus 66.7%, p  = 0.021). The overall incidence rate of adverse events was 44.4%, with fatigue being the most common (13.0%). Conclusion. SOF-based DAAs regimen can achieve ideal SVR12 for Chinese patients with both GT3a and GT6a HCV infection. The tolerance and safety of SOF-based DAAs regimen are good.

Efficacy of Direct-Acting Antiviral Combination Therapy in the Treat-ment of Hepatitis C Virus Among Kidney Transplant Patients

2020 ◽  
Vol 18 ◽  
Author(s):  
Mohammed Al Atbee ◽  
Saad Shaheen Al-Taher ◽  
Majid Alabbood
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Infection ◽  
Kidney Transplant ◽  
Virological Response ◽  
Hepatitis C Virus Infection ◽  
Direct Acting Antiviral ◽  
Transplant Patients ◽  
Kidney Transplant Patients ◽  
Direct Acting

Background: Up to date, there is no consensus on the best combination of direct-acting antiviral to treat hepatitis C virus in kidney transplant recipients. Objective: This study aims to analyze the efficacy of combination of sofosbuvir and ledipasvir regimen for treatment of hepatitis C virus infected kidney transplant patients. Method: A cross-sectional study conducted in a nephrology clinic and the Nephrology Center in Basrah Teaching Hospital from June 2015 to June 2018. Ledifos (90 mg Ledipasvir and 400 mg Sofosbuvir fixed-dose) was given as a single daily dose for all the participants for 12 weeks. Response for therapy was tested by follow up hepatitis C virus load at the end of 12 weeks and 24 weeks. The sustained virological response was defined as negative viral load of hepatitis C virus (aviremia) at the end of therapy. This study was done according to the Helsinki Congress. Results: A total of 60 (16 females) patients with renal transplantation and hepatitis C virus infection were included. Mean age was 40±6.2 years. A sustained virological response observed in all of the patients who received Ledifos after 12 and 24 weeks of therapy for all genotypes (1a, 1b and 4); p= 0.0001. Genotype 1a was more prevalent among males, 34 (56.6%); p= 0.0001, and it was the most common genotype tested negative serologically, 11 (18.3%). Conclusion: Ledifos therapy is effective and safe option for the treatment of hepatitis C virus infection in the post–renal transplant setting.

Effect on the adherence to concomitant medications after initiation of treatment with direct-acting antiviral agents against hepatitis C virus

2020 ◽  
Vol 43 (8) ◽  
pp. 418-425
Author(s):  
Maria Isabel Guzman Ramos ◽  
Mercedes Manzano-García ◽  
M. de las Aguas Robustillo-Cortés ◽  
Juan Antonio Pineda ◽  
Ramón Morillo-Verdugo
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Agents ◽  
Direct Acting Antiviral ◽  
Concomitant Medications ◽  
Direct Acting ◽  
Direct Acting Antiviral Agents

scholarly journals Computer-aided identification of a series of novel ligands showing high potency as hepatitis C virus NS3/4A protease inhibitors

2021 ◽  
Vol 45 (1) ◽  
Author(s):  
Stephen Ejeh ◽  
Adamu Uzairu ◽  
Gideon Adamu Shallangwa ◽  
Stephen E. Abechi
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Binding Energy ◽  
Protease Inhibitor ◽  
Protease Inhibitors ◽  
Antiviral Agents ◽  
High Potency ◽  
Direct Acting Antiviral ◽  
Direct Acting ◽  
Direct Acting Antiviral Agents

Abstract Background Hepatitis C virus (HCV) is a global medical condition that causes several life-threatening chronic diseases in the liver. The conventional interferon-free treatment regimens are currently in use by a blend of direct-acting antiviral agents (DAAs) aiming at the viral NS3 protease. However, major concerns may be the issue of DAA-resistant HCV strains and the limited availability to the DAAs due to their high price. Due to this crisis, the developments of a new molecule with high potency as an NS3/4A protease inhibitor of the hepatitis-C virus remain a high priority for medical research. This study aimed to use in-silico methods to identify high potent molecule as an NS3/4A protease inhibitor and investigating the binding energy of the identified molecule in comparison with approved direct-acting antiviral agents (Telaprevir, Simeprevir, and Voxilaprevir) through molecular docking. Results The model obtained by in-silico method have the following statistical records, coefficient of determination (r2) of 0.7704, cross-validation (q2LOO = 0.6914); external test set (r2(pred) = 0.7049) and Y-randomization assessment (cR2p = 0.7025). The results from the model were used to identify 12 new potential human HCV NS3/4A protease inhibitors, and it was observed that the identified molecule is well-fixed when docked with the receptor and was found to have the lowest binding energy of − 10.7, compared to approved direct-acting antiviral agents (Telaprevir, Simeprevir, and Voxilaprevir) with − 9.5, − 10.0, − 10.5 binding energy, respectively. Conclusion The binding affinity (− 10.7) of the newly identified molecule docked with 3D structures of HCV NS3/4a protease/helicase (PDB ID: 4A92) was found to be better than that of Telaprevir, Simeprevir, and Voxilaprevir (approved direct-acting antiviral agents) which are − 9.5, − 10.0, and − 10.5, respectively. Hence, a novel molecule was identified showing high potency as HCV NS3/4a protease inhibitors.

scholarly journals Hepatitis C virus vaccine development: old challenges and new opportunities

2015 ◽  
Vol 2 (3) ◽  
pp. 285-295 ◽  
Author(s):  
Dapeng Li ◽  
Zhong Huang ◽  
Jin Zhong
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Vaccine Development ◽  
Rna Virus ◽  
Antiviral Agents ◽  
Resistance Mutations ◽  
Direct Acting Antiviral ◽  
Direct Acting

Abstract Hepatitis C virus (HCV), an enveloped positive-sense single-stranded RNA virus, can cause chronic and end-stage liver diseases. Approximately 185 million people worldwide are infected with HCV. Tremendous progress has been achieved in the therapeutics of chronic hepatitis C thanks to the development of direct-acting antiviral agents (DAAs), but the worldwide use of these highly effective DAAs is limited due to their high treatment cost. In addition, drug-resistance mutations remain a potential problem as DAAs are becoming a standard therapy for chronic hepatitis C. Unfortunately, no vaccine is available for preventing new HCV infection. Therefore, HCV still imposes a big threat to human public health, and the worldwide eradication of HCV is critically dependent on an effective HCV vaccine. In this review, we summarize recent progresses on HCV vaccine development and present our views on the rationale and strategy to develop an effective HCV vaccine.

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