R 1626, a novel nucleoside analogue, has produced encouraging antiviral activity in patients with hepatitis C virus (HCV) infection.

2008 ◽  
Vol &NA; (1658) ◽  
pp. 9
Author(s):  
&NA;
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Activity ◽  
Nucleoside Analogue ◽  
Hcv Infection

scholarly journals Preclinical Characterization of the Novel Hepatitis C Virus NS3 Protease Inhibitor GS-9451

2013 ◽  
Vol 58 (2) ◽  
pp. 647-653 ◽  
Author(s):  
Huiling Yang ◽  
Margaret Robinson ◽  
Amoreena C. Corsa ◽  
Betty Peng ◽  
Guofeng Cheng ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Activity ◽  
Protease Inhibitor ◽  
Hcv Infection ◽  
Cross Resistance ◽  
Protease Gene ◽  
Ns5a Inhibitor ◽  
Ns3 Protease

ABSTRACTGS-9451 is a selective hepatitis C virus (HCV) NS3 protease inhibitor in development for the treatment of genotype 1 (GT1) HCV infection. Key preclinical properties of GS-9451, includingin vitroantiviral activity, selectivity, cross-resistance, and combination activity, as well as pharmacokinetic properties, were determined. In multiple GT1a and GT1b replicon cell lines, GS-9451 had mean 50% effective concentrations (EC50s) of 13 and 5.4 nM, respectively, with minimal cytotoxicity; similar potency was observed in chimeric replicons encoding the NS3 protease gene of GT1 clinical isolates. GS-9451 was less active in GT2a replicon cells (EC50= 316 nM). Additive to synergisticin vitroantiviral activity was observed when GS-9451 was combined with other agents, including alpha interferon, ribavirin, and the polymerase inhibitors GS-6620 and tegobuvir (GS-9190), as well as the NS5A inhibitor ledipasvir (GS-5885). GS-9451 retained wild-type activity against multiple classes of NS5B and NS5A inhibitor resistance mutations. GS-9451 was stable in hepatic microsomes and hepatocytes from human and three other tested species. Systemic clearance was low in dogs and monkeys but high in rats. GS-9451 showed good oral bioavailability in all three species tested. In rats, GS-9451 levels were ∼40-fold higher in liver than plasma after intravenous dosing, and elimination of GS-9451 was primarily through biliary excretion. Together, these results are consistent with the antiviral activity observed in a recent phase 1b study. The results ofin vitrocross-resistance and combination antiviral assays support the ongoing development of GS-9451 in combination with other agents for the treatment of chronic HCV infection.

scholarly journals Ribavirin Antagonizes the In Vitro Anti-Hepatitis C Virus Activity of 2′-C-Methylcytidine, the Active Component of Valopicitabine

2006 ◽  
Vol 50 (10) ◽  
pp. 3444-3446 ◽  
Author(s):  
Lotte Coelmont ◽  
Jan Paeshuyse ◽  
Marc P. Windisch ◽  
Erik De Clercq ◽  
Ralf Bartenschlager ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Activity ◽  
Protease Inhibitor ◽  
Nucleoside Analogue ◽  
Active Component ◽  
Pyrimidine Nucleoside ◽  
Virus Activity ◽  
Hcv Protease

ABSTRACT Ribavirin antagonizes the in vitro anti-hepatitis C virus (HCV) activity of the pyrimidine nucleoside analogue 2′-C-methylcytidine, the active component of the experimental anti-HCV drug valopicitabine. In contrast, the combination of ribavirin with either the purine nucleoside analogue 2′-C-methyladenosine or the HCV protease inhibitor VX-950 resulted in an additive antiviral activity. These findings may have implications when planning clinical studies with valopicitabine.

scholarly journals Identification of Three Interferon-Inducible Cellular Enzymes That Inhibit the Replication of Hepatitis C Virus

2007 ◽  
Vol 82 (4) ◽  
pp. 1665-1678 ◽  
Author(s):  
Dong Jiang ◽  
Haitao Guo ◽  
Chunxiao Xu ◽  
Jinhong Chang ◽  
Baohua Gu ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Amino Acid ◽  
Protein Kinase ◽  
Antiviral Activity ◽  
Underlying Mechanism ◽  
Hcv Infection ◽  
Antiviral Effects ◽  
Huh7 Cells ◽  
Aromatic Amino Acid Residue

ABSTRACT Hepatitis C virus (HCV) infection is a common cause of chronic hepatitis and is currently treated with alpha interferon (IFN-α)-based therapies. However, the underlying mechanism of IFN-α therapy remains to be elucidated. To identify the cellular proteins that mediate the antiviral effects of IFN-α, we created a HEK293-based cell culture system to inducibly express individual interferon-stimulated genes (ISGs) and determined their antiviral effects against HCV. By screening 29 ISGs that are induced in Huh7 cells by IFN-α and/or up-regulated in HCV-infected livers, we discovered that viperin, ISG20, and double-stranded RNA-dependent protein kinase (PKR) noncytolytically inhibited the replication of HCV replicons. Mechanistically, inhibition of HCV replication by ISG20 and PKR depends on their 3′-5′ exonuclease and protein kinase activities, respectively. Moreover, our work, for the first time, provides strong evidence suggesting that viperin is a putative radical S-adenosyl-l-methionine (SAM) enzyme. In addition to demonstrating that the antiviral activity of viperin depends on its radical SAM domain, which contains conserved motifs to coordinate [4Fe-4S] cluster and cofactor SAM and is essential for its enzymatic activity, mutagenesis studies also revealed that viperin requires an aromatic amino acid residue at its C terminus for proper antiviral function. Furthermore, although the N-terminal 70 amino acid residues of viperin are not absolutely required, deletion of this region significantly compromises its antiviral activity against HCV. Our findings suggest that viperin represents a novel antiviral pathway that works together with other antiviral proteins, such as ISG20 and PKR, to mediate the IFN response against HCV infection.

Position Paper on Treatment of Hepatitis C in Romania, 2017. Part One

2017 ◽  
Vol 26 (2) ◽  
pp. 171-181 ◽  
Author(s):  
Liana Gheorghe ◽  
Ioan Sporea ◽  
Speranţa Iacob ◽  
Roxana Şirli ◽  
Anca Trifan ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Liver Disease ◽  
Hepatitis C ◽  
Limit Of Detection ◽  
Position Paper ◽  
Hcv Infection ◽  
Fixed Dose ◽  
Diagnostic Tools ◽  
End Stage Liver Disease ◽  
End Stage

Background & Aims: Hepatitis C Virus (HCV) infection is a common condition with endemic prevalence in some areas of the world. In Romania, the mean prevalence is about 3%. New treatments became available on the market in recent years and new drugs are in the pipeline. A re-evaluation of HCV therapy was considered mandatory. The Romanian Society of Gastroenterology and Hepatology undertook this task for the practitioners of this country.Methodology: A group of recognized experts was created who screened the available literature and the major available guidelines. A list of items requiring attention has been created. These items were discussed and rated. Decisions were taken by consensus.Recommendations: We present here the first of the two parts of our Society’s recommendations for chronic HCV infection treatment. An agreement was reached regarding the diagnostic tools, the assessment of severity and the up-dated therapy schedules.Conclusions: This Position Paper represents a guide for the assessment and the therapy of HCV infection. The recommendations are in concordance with other guidelines but are applied to the real-life conditions in this country.Abbreviations: DAAs: Direct-acting antivirals; DDIs: Drug-drug interactions; ESLD: End-stage liver disease; ESRD: End-stage renal disease; eGFR: Estimated glomerular filtration rate; EASL: European Association for the Study of the Liver; EMA: European Medicines Agency; FDA: US Food and Drug Administration; FDC: Fixed-dose combination; GT: Genotype; GRADE: Grading of Recommendations Assessment, Development and Evaluation; HCV: Hepatitis C virus; HCC: Hepatocellular carcinoma; LT: Liver transplantation; LLD: Lower limit of detection; MELD score: Mayo-Clinic End-Stage Liver Disease score; ANMDM: National Agency of Medicines and Medical Devices; PPIs: Proton pump inhibitors; PWID: People who inject drugs; RCT: Randomized controlled trial; RDT: Rapid diagnostic test; RAS: Resistance-associated substitution; SRGH: Romanian Society of Gastroenterology and Hepatology; SAE: serious adverse events; SPC: Summary of Product Characteristics; SVR: Sustained virologic response.

Position Paper on Treatment of Hepatitis C in Romania 2017. Part Two

2017 ◽  
Vol 26 (3) ◽  
pp. 309-317 ◽  
Author(s):  
Liana Gheorghe ◽  
Ioan Sporea ◽  
Speranța Iacob ◽  
Roxana Șirli ◽  
Anca Trifan ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Liver Disease ◽  
Hepatitis C ◽  
Sustained Virologic Response ◽  
Real Life ◽  
Virologic Response ◽  
Position Paper ◽  
Hcv Infection ◽  
End Stage Liver Disease ◽  
End Stage

Background & Aims: Hepatitis C virus (HCV) infection is a common condition with endemic prevalence in some areas of the world. In Romania, the mean prevalence is about 3%. New treatments have become available on the market in recent years and new drugs are in the pipeline. A re-evaluation of HCV therapy was considered mandatory. The Romanian Society of Gastroenterology and Hepatology undertook this task for the practitioners of this country.Methodology: A group of recognized experts was created who screened the available literature and the major available guidelines. A list of items requiring attention was created and these were discussed and rated. Decisions were taken by consensus.Recommendations: We present here the second part of the Society’s recommendations for chronic HCV infection treatment. An agreement between experts was reached regarding the therapy of the special categories of patients infected with HCV, complications and monitoring of the therapy, follow-up of the patients who reached sustained virologic response and re-treatment of the patients with therapy failure.Conclusions: This Position Paper represents a guide for the assessment and the therapy of HCV infection. The recommendations are in concordance with other guidelines but are applied to real-life conditions in Romania. Abbreviations: CKD: Chronic kidney disease; DAAs: Direct-acting antivirals; DDIs: Drug-drug interactions; ESDL: End-stage liver disease; FCH: Fibrosing cholestatic hepatitis; GT: Genotype; HCV: Hepatitis C virus; HCC: Hepatocellular carcinoma; LT: Liver transplantation; MELD score: Mayo-Clinic End-Stage Liver Disease score; PDC: Premature discontinuation; PWID: Persons who inject drugs; RASs: Resistance associated substitutions; RBV: Ribavirin; RCT: Randomized controlled trial; SAE: Serious adverse events; SRGH: Romanian Society of Gastroenterology and Hepatology; SVR: Sustained virologic response.

Prevalence and Risk Factors of Hepatitis C Virus (HCV) in Tehsil Batkhela District Malakand, KPK, Pakistan

2018 ◽  
Vol 9 (06) ◽  
pp. 20251-20256
Author(s):  
Mudassir Khan ◽  
Shahrukh Khan ◽  
Shohra Haider ◽  
Fazal Jalil ◽  
Muhsin Jamal ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Skin Color ◽  
Significant Risk ◽  
Rapid Test ◽  
Prevalence Ratio ◽  
Hcv Infection ◽  
Hcv Rna ◽  
Common Symptom

Background: Prevalence of Hepatitis C viral infection and its major risk factors has been found out in population of Batkhela, Khyber Pakhtunkhwa, Pakistan by taking number of volunteers from the interested area. HCV prevalence has not been researched in recent time here in this area, so that’s why we contributed. Materials and Methods: Ab rapid test cassette serum/plasma (USA) kit has been used for the mentioned purpose following by ELISA and finally PCR to find out active infection of virus. ICT positive individuals were reconfirmed by ELISA and then ELISA positive samples were carefully investigated by RT-PCR for Hepatitis C Virus. Results: The study population was of 770 volunteers belonging to the mentioned area of research, 453 males and 317 females. The overall prevalence was found to be 5.32% of HCV in Batkhela. This prevalence ratio was 3.12% in males and 2.20 % in females. 3rd generation ELISA was used to refine ICT positive samples which showed that 37 of the ICT positive samples had antibodies detected by ELISA. To find out active HCV infection, ELISA positive samples were refined by real time PCR which showed 2.98% of prevalence of active HCV infection in Batkhela based on HCV RNA in their blood. Principle Conclusion: Overall prevalence was found 5.32%, contaminated reused syringes and blades at Barbour’s shop, blood transfusion, surgical operations and unhygienic food in stalls etc were found significant risk factors for acquiring HCV infection. Body weakness and pale yellow skin color was common symptom in HCV positive volunteers. Safe sexual activities, blood screening before donation and sterilizing surgical equipment’s can protect us from Hepatitis C Virus.

Genetic polymorphisms as the predictors of response to antiviral treatment in chronic hepatitis C virus infection

2011 ◽  
Vol 152 (22) ◽  
pp. 876-881
Author(s):  
Alajos Pár
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Genetic Polymorphisms ◽  
Chronic Hepatitis C ◽  
Genome Wide Association Study ◽  
Antiviral Treatment ◽  
Hcv Infection ◽  
Snp Analysis ◽  
Chronic Hcv

The review discusses the genetic polymorphisms involved in the pathogenesis of hepatitis C virus (HCV) infection, that may determine the outcome of disease. In this field earlier both certain major histocompatibility complex (MHC) alleles and some cytokine gene variants have also been studied. Recently, the genome-wide association study (GWAS) and targeted single nucleotide polymorphism (SNP) analysis have revealed that a variant in the promoter region of interleukin-28B (IL-28B) gene is strongly linked to viral clearance and it may be the strongest pretreatment predictor of treatment response in chronic hepatitis C. Last year it was shown that two genetic variants leading to inosine triphosphatase deficiency protect against haemolytic anemia in patients receiving ribavirin during antiviral treatment for chronic HCV infection. Orv. Hetil., 2011, 152, 876–881.

A Serological Storm

1970 ◽  
Vol 9 (2) ◽  
Author(s):  
Bertha Wong MD ◽  
Maria Bagovich MD ◽  
Ivan Blasutig PhD ◽  
Simon Carette MD MPhil
Keyword(s):  
Differential Diagnosis ◽  
Hepatitis C Virus ◽  
Immune System ◽  
Hepatitis C ◽  
Hcv Infection ◽  
Clinical Context ◽  
Autoantibody Profile ◽  
Life Threatening ◽  
Clinically Significant ◽  
Sensory Polyneuropathy

This article describes a patient presenting with a sensory polyneuropathy and multiple autoantibodies, leading to the diagnosis of hepatitis C virus (HCV) infection. His widely positive autoantibody profile in the absence of clinically significant rheumatic disease illustrates the importance of interpreting autoimmune serology in the appropriate clinical context and the concept of HCV being a non-specific activator of the immune system. In addition, it highlights the importance of considering untreated HCV infection in the differential diagnosis of rheumatic complaints, particularly if the workup reveals multiple autoantibodies, as HCV is a potentially severe and life-threatening disease, which can be appropriately managed with effective antiviral therapy.

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