Journal of Applied Molecular Cell Biology


ISSN: 2412-2580
Short Key Title: J App Mol Cell Bio
DOI: http://dx.doi.org/10.21065/24122580
Start Year: 2014

THE CURRENT CHALLENGE OF HCV-RNA RESISTANCE AGAINST DIRECT-ACTING ANTIVIRAL DRUGS.
Nida Taha, Bashir Ahmad
1. M.Phil (Pharmacology) Scholar, Riphah Institute of Pharmaceutical Sciences, Ripah International University Lahore, Pakistan. 2. Professor of Pharmacology, Riphah Institute of Pharmaceutical Sciences, Ripah International University Lahore, Pakistan.
Keywords: HCV-RNA, Resistance, Direct-Acting Antiviral.
Abstract

The HCV-RNA (Hepatitis-C RNA) diagnosed patients are recommended interferon free Direct-Acting Antiviral (DAAs) therapy. Although the treated patients are reported viral resistance to DAAs, the genotype 3a infection is challenge to NS5A inhibitors leading to cirrhosis. Therefore, the patients with chronic Hepatitis-C treated with DAAs, nucleotide analogue inhibitors or NS5B protein have high risk of resistance. Breakthrough or relapse is not common with these drugs when used as monotherapy.NS3-4A protease inhibitors and non-nucleoside inhibitors have low susceptibility to resistance. Sofosbuvir-resistant variants have been discovered that disappear after treatment withdrawal. Patients who experience relapse after an INF-free treatment have large fraction of drug resistant viruses.

Article Information

Identifiers and Pagination:
Year:2018
Volume:5
First Page:1
Last Page:2
Publisher Id:J App Mol Cell Bio (2018 ). 5. 1-2
Article History:
Received:Nov. 13, 2018
Accepted:Dec. 17, 2017
Collection year:2018
First Published:Dec. 21, 2018

The HCV-RNA (Hepatitis-C RNA) diagnosed patients are recommended interferon free Direct-Acting Antiviral (DAAs) therapy. Although the treated patients are reported viral resistance to DAAs, the genotype 3a infection is challenge to NS5A inhibitors leading to cirrhosis. Therefore, the patients with chronic Hepatitis-C treated with DAAs, nucleotide analogue inhibitors or NS5B protein have high risk of resistance. Breakthrough or relapse is not common with these drugs when used as monotherapy.NS3-4A protease inhibitors and non-nucleoside inhibitors have low susceptibility to resistance. Sofosbuvir-resistant variants have been discovered that disappear after treatment withdrawal. Patients who experience relapse after an INF-free treatment have large fraction of drug resistant viruses. [1].

The quantification of Hepatitis-C RNA has been made possible by means of commercial and standardized assays in mid 90’s. These assays were used in retrospective and prospective cohort studies and also used in clinical trials. Currently, the most diagnostic and research laboratories used Real Time PCR (RT-PCR) based assays. In theory these methods give better analytical sensitivity, improved sensitivity, broader dynamic ranges of quantification, precision and reproducibility. [2,3] RT-PCR methods can detect and quantify minute amounts of circulating HCV RNA i.e, 12 IU/ml. This technique is used to assess the response to antiviral therapy. [4]

Genotype 3 infections can cause rapid development to cirrhosis and increased rates of hepatocellular carcinomas than other genotypes. Patients with genotype 3 infection have lower sustained virologic response rates than other genotypes treated with DAAs. Antiviral treatment for hepatitis C is changing rapidly. [5] Current therapy is based on direct acting antiviral agents due to their efficacy, improved safety and sustained virologic response. Though some patients show resistance to therapy.

References

1.       Kohli A., & Shaffer A. Treatment of hepatitis C: a systemic review. Journal of the American  Medical Association, 2014; 13;312(6). 631-40.

2.       McEwan P., & Webster S. Estimating the cost-effectiveness of daclatasvir + sofosbuvir versus sofosbuvir + ribavirin for patients with genotype 3 hepatitis C virus. Japan Society of Hepatology, 2017; 46(5), 423-33.

3.       Nitulescu R, Young J, Saeed S, Cooper C, Cox J, Martel-Laferriere V, Hull M, Walmsley S, Tyndall M, Wong A, Klein MB; Canadian Co-Infection Cohort Study. Variation in hepatitis C virus treatment uptake between Canadian centres in the era of direct-acting antivirals. Int J Drug Policy. 2018 Dec 26;65:41-49. doi: 10.1016/j.drugpo.2018.08.012.

4.       Patoli BB, Patoli AA, Balani NK, Korejo AA. Molecular surveillance of HCV mono-infection and HCV-HBV co-infection in symptomatic population at Hyderabad, Pakistan. Afr Health Sci. 2018 Sep;18(3):531-538. doi: 10.4314/ahs.v18i3.9. PubMed PMID: 30602984; PubMed Central PMCID: PMC6307001.

Skladany L, Janceková D, Svac J. Hepatitis C virus antibodies in outpatients with chronic kidney disease. Clin Exp Hepatol. 2018 Dec;4(4):267-270. doi: 10.5114/ceh.2018.80129


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Editor in Chief
Bruno Perillo  (PhD)
Istituto di Scienze dell, Alimentazione, Consiglio Nazionale delle Ricerche, via Roma, 52, 83100 Avellino, Italy.

Bibliography

Dr. Bruno Perillo PhD is associated with Istituto di Scienze dell, Alimentazione, Consiglio Nazionale delle Ricerche, via Roma, 52, 83100 Avellino, Italy. He has contributed in book chapter entitled “Analysis of posttranslational modifications in the control of chromatin plasticity observed at estrogen-responsive sites in human breast cancer cells” Methods Mol. Biol. 1204, 59-69. 2014. Whereas, his research work is published in renowned credible journals.  

Journal Highlights
Abbreviation: J App Mol Cell Bio
doi: http://dx.doi.org/10.21065/24122580
Frequency: Annual
Current Volume: 4 (2017)
Next volume: December, 2018 (Volume 5)
Back volumes: 1-4
Starting year: 2014
Nature: Online
Submission: Online
Language: English

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  • Allele-specific oligonucleotide

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