scholarly journals Pro: Use of Hepatitis C Virus-Positive Donors Should Be Considered Standard of Care

2018 ◽  
Vol 12 (4) ◽  
pp. 100-104 ◽  
Author(s):  
William A. Werbel ◽  
Christine M. Durand
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Standard Of Care

scholarly journals Hepatitis C Virus NS3 Inhibitors: Current and Future Perspectives

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Kazi Abdus Salam ◽  
Nobuyoshi Akimitsu
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Protease Inhibitors ◽  
Standard Of Care ◽  
Pegylated Interferon ◽  
Virologic Response ◽  
Hcv Infection ◽  
Main Concern ◽  
Pegylated Interferon Plus Ribavirin ◽  
Direct Acting

Currently, hepatitis C virus (HCV) infection is considered a serious health-care problem all over the world. A good number of direct-acting antivirals (DAAs) against HCV infection are in clinical progress including NS3-4A protease inhibitors, RNA-dependent RNA polymerase inhibitors, and NS5A inhibitors as well as host targeted inhibitors. Two NS3-4A protease inhibitors (telaprevir and boceprevir) have been recently approved for the treatment of hepatitis C in combination with standard of care (pegylated interferon plus ribavirin). The new therapy has significantly improved sustained virologic response (SVR); however, the adverse effects associated with this therapy are still the main concern. In addition to the emergence of viral resistance, other targets must be continually developed. One such underdeveloped target is the helicase portion of the HCV NS3 protein. This review article summarizes our current understanding of HCV treatment, particularly with those of NS3 inhibitors.

scholarly journals Preclinical Characterization of GSK2336805, a Novel Inhibitor of Hepatitis C Virus Replication That Selects for Resistance in NS5A

2013 ◽  
Vol 58 (1) ◽  
pp. 38-47 ◽  
Author(s):  
Jill Walker ◽  
Renae Crosby ◽  
Amy Wang ◽  
Ermias Woldu ◽  
Jessica Vamathevan ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Standard Of Care ◽  
Cross Resistance ◽  
Current Standard ◽  
Dna Viruses ◽  
Consensus Sequences ◽  
Genotype 1A ◽  
Rna And Dna

ABSTRACTGSK2336805 is an inhibitor of hepatitis C virus (HCV) with picomolar activity on the standard genotype 1a, 1b, and 2a subgenomic replicons and exhibits a modest serum shift. GSK2336805 was not active on 22 RNA and DNA viruses that were profiled. We have identified changes in the N-terminal region of NS5A that cause a decrease in the activity of GSK2336805. These mutations in the genotype 1b replicon showed modest shifts in compound activity (<13-fold), while mutations identified in the genotype 1a replicon had a more dramatic impact on potency. GSK2336805 retained activity on chimeric replicons containing NS5A patient sequences from genotype 1 and patient and consensus sequences for genotypes 4 and 5 and part of genotype 6. Combination and cross-resistance studies demonstrated that GSK2336805 could be used as a component of a multidrug HCV regimen either with the current standard of care or in combination with compounds with different mechanisms of action that are still progressing through clinical development.

scholarly journals Structural and Antigenic Definition of Hepatitis C Virus E2 Glycoprotein Epitopes Targeted by Monoclonal Antibodies

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Giuseppe Sautto ◽  
Alexander W. Tarr ◽  
Nicasio Mancini ◽  
Massimo Clementi
Keyword(s):  
Immune Response ◽  
Monoclonal Antibodies ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Structural Characteristics ◽  
Standard Of Care ◽  
Surface Glycoprotein ◽  
Current Standard ◽  
Humoral Immune ◽  
Promising Tool

Hepatitis C virus (HCV) is the major cause of chronic liver disease as well as the major indication for liver transplantation worldwide. Current standard of care is not completely effective, not administrable in grafted patients, and burdened by several side effects. This incomplete effectiveness is mainly due to the high propensity of the virus to continually mutate under the selective pressure exerted by the host immune response as well as currently administered antiviral drugs. The E2 envelope surface glycoprotein of HCV (HCV/E2) is the main target of the host humoral immune response and for this reason one of the major variable viral proteins. However, broadly cross-neutralizing monoclonal antibodies (mAbs) directed against HCV/E2 represent a promising tool for the study of virus-host interplay as well as for the development of effective prophylactic and therapeutic approaches. In the last few years many anti-HCV/E2 mAbs have been evaluated in preclinical and clinical trials as possible candidate antivirals, particularly for administration in pre- and post-transplant settings. In this review we summarize the antigenic and structural characteristics of HCV/E2 determined through the use of anti-HCV/E2 mAbs, which, given the absence of a crystal structure of this glycoprotein, represent currently the best tool available.

scholarly journals Combination of a Hepatitis C Virus NS3-NS4A Protease Inhibitor and Alpha Interferon Synergistically Inhibits Viral RNA Replication and Facilitates Viral RNA Clearance in Replicon Cells

2004 ◽  
Vol 48 (12) ◽  
pp. 4784-4792 ◽  
Author(s):  
Kai Lin ◽  
Ann D. Kwong ◽  
Chao Lin
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Adverse Effects ◽  
Protease Inhibitor ◽  
Standard Of Care ◽  
Rna Replication ◽  
Viral Rna ◽  
Alpha Interferon ◽  
Hcv Rna

ABSTRACT The present standard of care for hepatitis C virus (HCV) infection is pegylated alpha interferon (IFN-α) in combination with ribavirin. However, specific antivirals such as HCV NS3-NS4A protease inhibitors are now in clinical development, and these agents can potentially be used in combination with the present treatments. Therefore, it is important to investigate the potential benefits or adverse effects of these new combinations by using available in vitro HCV culture systems first. In the present study we demonstrate that the combination of a specific HCV NS3-NS4A protease inhibitor and IFN-α synergistically inhibits HCV RNA replication in replicon cells, with little or no increase in cytotoxicity. Furthermore, the benefit of the combination was sustained over time, such that a greater than 3-log reduction in HCV RNA levels was achieved following 9 days of treatment. The viral RNA appeared to be cleared from the replicon cells after 14 days of treatment, and no viral RNA rebound was observed upon withdrawal of the inhibitors. In each case, the antiviral effects obtained with higher concentrations of either the protease inhibitor alone or IFN-α alone can be achieved by a combination of both agents at lower concentrations, which may potentially reduce the risk of possible adverse effects associated with high doses of either agent.

Trends in the Treatment of Chronic Hepatitis C Virus Infection

2009 ◽  
Vol 22 (4) ◽  
pp. 405-418 ◽  
Author(s):  
Jennifer J. Kiser
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Liver Disease ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Standard Of Care ◽  
New Drugs ◽  
Current Standard ◽  
Course Of Illness ◽  
Chronic Hepatitis C Virus

Despite reductions in the incidence of new hepatitis C virus infections, infections from previous decades continue to place a substantial burden on our health care system. Although the course of the disease is highly variable, approximately 20% to 30% of patients develop cirrhosis, end-stage liver disease, or hepatocellular carcinoma. Fortunately, treatment with our current standard of care, peginterferon a and ribavirin, can reduce the complications of chronic liver disease. However, these drugs are associated with significant adverse effects, many patients are ineligible for treatment, and only 50% are cured. Thus, there is a tremendous need to improve our current therapies and develop new compounds for this disease. This review highlights the transmission, pathophysiology, and course of illness; the pharmacokinetics, proposed mechanisms of action, adverse events, and potential drug interactions with peginterferon a and ribavirin; current treatment trends; the role of the pharmacist in the treatment of this disease; and investigational drugs in later stages of clinical development. Despite the initial hope that these new drugs would replace our current standard of care, it has become clear that ribavirin and peginterferon a will continue to play an important role in the treatment of chronic hepatitis C virus in the years to come.

scholarly journals Sequencing Analysis of NS3/4A, NS5A, and NS5B Genes from Patients Infected with Hepatitis C Virus Genotypes 5 and 6

2016 ◽  
Vol 54 (7) ◽  
pp. 1835-1841 ◽  
Author(s):  
Karin S. Ku ◽  
Ramakrishna K. Chodavarapu ◽  
Ross Martin ◽  
Michael D. Miller ◽  
Hongmei Mo ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Pcr Amplification ◽  
Standard Of Care ◽  
Sequencing Analysis ◽  
Sequencing Data ◽  
Hcv Genotype ◽  
Standard Of Care Treatment ◽  
Genotype 5 ◽  
Direct Acting

Direct-acting antivirals (DAAs) with activity against multiple genotypes of the hepatitis C virus (HCV) were recently developed and approved for standard-of-care treatment. However, sequencing assays to support HCV genotype 5 and 6 analysis are not widely available. Here, we describe the development of a sequencing assay for the NS3/4A, NS5A, and NS5B genes from HCV genotype 5 and 6 patient isolates. Genotype- and subtype-specific primers were designed to target NS3/4A, NS5A, and NS5B for cDNA synthesis and nested PCR amplification. Amplification was successfully performed for a panel of 32 plasma samples from HCV-infected genotype 5 and 6 patients with sequencing data obtained for all attempted samples. LiPA 2.0 (Versant HCV genotype 2.0) is a reverse hybridization line probe assay that is commonly used for genotyping HCV-infected patients enrolled in clinical studies. Using NS3/4A, NS5A, and NS5B consensus sequences, HCV subtypes were determined that were not available for the initial LiPA 2.0 result for genotype 6 samples. Samples amplified here included the following HCV subtypes: 5a, 6a, 6e, 6f, 6j, 6i, 6l, 6n, 6o, and 6p. The sequencing data generated allowed for the determination of the presence of variants at amino acid positions previously characterized as associated with resistance to DAAs. The simple and robust sequencing assay for genotypes 5 and 6 presented here may lead to a better understanding of HCV genetic diversity and prevalence of resistance-associated variants.

scholarly journals An Open Labelled, Active Controlled, Three-Arm, Parallel-Group study of the safety and efficacy of the oral formulation of Oral Iodine Complex (RENESSANS) administered alone and in combination with standard interferon therapy in patients suffering from Chronic HCV Hepatitis

2020 ◽  
Author(s):  
Ghiasun Nabi ◽  
Muhammad Nasir ◽  
Ghias ulhasan ◽  
Israr Toor ◽  
Fawad Zia ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virological Response ◽  
Standard Of Care ◽  
Safety And Efficacy ◽  
Iodine Complex ◽  
Parallel Group Study ◽  
Parallel Group ◽  
Chronic Hcv ◽  
Iodine Complexes

AbstractIodine has strong antimicrobial properties and has been used in topical applications as antiseptic. Its systemic use in form of iodine complexes derived from dried seaweed extract is beneficial in treating various disorders. Hepatitis C Virus (HCV) chronic infection is present in 6-10% of the Pakistani population and is a major healthcare burden that could benefit from innovative therapeutic regimens.ObjectiveA pilot study has shown the safety and efficacy of iodine complexes in chronic Hepatitis C virus infection. and this clinical study is aimed to further explore the previous findings.MethodsThis is an open-labeled, active-controlled, three-arm, parallel-group study including 90 patients of chronic HCV infection with each arm having 30 patients. The patient groups received 15mg/day iodine complex only, the standard of care therapy interferon+ribavirin, and iodine complex in combination with interferon+ribavirin regimen for 6 months. Efficacy assessment will base upon post-treatment Rapid Virological Response (RVR) at 4 weeks, Early Virological Response (EVR) at 12 weeks, and End of Treatment Viral Response (ETR) at 24/48 weeks.ResultsAs only 3.33% of patients showed at the ETR with iodine complex alone, combination with interferon+ribavirin showed significant improvement in comparison to interferon+ribavirin alone. Iodine complex+ interferon+ribavirin showed 80% RVR and 90% ETR while the standard of care therapy showed 66.7% RVR and 76.67% ETR, respectively. No additional adverse events of iodine complex were observed.ConclusionIodine complex showed a significant synergistic effect when combined interferon+ribavirin regimen and could be useful in relapsers and non-responders.

scholarly journals Thrombocytopenia in Egyptian Patients with Hepatitis C Virus Treated with Standard of Care Therapy: A Cohort Study

2014 ◽  
Vol 4 (12) ◽  
pp. 1254-1267
Author(s):  
Eman Medhat ◽  
Gamal Esmat ◽  
Mohamed Seif ◽  
Mohammed El-Beshlawy ◽  
Raghda Marzaban ◽  
...  
Keyword(s):  
Cohort Study ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Standard Of Care ◽  
Egyptian Patients
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