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Hepatitis C Viral RNA NS3 Genotype

Test code(s) 90924

This is an outdated version of this FAQ. It was effective 03/12/2014 to 07/07/2015.

The current version is available here.

Question 1. What are hepatitis C virus (HCV) NS3 protease Inhibitors?

NS3 protease inhibitors are antiviral drugs. They are classified as direct acting agents (DAAs) and work by inhibiting the HCV NS3a protease.1-3 Clinical studies have shown that when NS3 protease inhibitors are combined with standard pegylated interferon (PEG) and ribavirin, a significantly higher proportion of patients achieve a sustained virologic response (SVR).1-3

Question 2. Which NS3 protease inhibitors are approved for clinical use?

Boceprevir (Victrelis®) and telaprevir (Incivek®)  were approved by the FDA in 2011 for the treatment of HCV genotype 1 patients.4,5 The newest protease inhibitor, simeprevir (Olysio™), was approved by the FDA in November 2013 for the same patient group.6 All three DAAs are intended for use as a component of a combination antiviral treatment regimen. Additional NS3 protease inhibitors are currently undergoing clinical trials.

Question 3. What methods are available to test for HCV NS3 protease inhibitor resistance?

A genotypic assay that uses reverse transcription of HCV RNA, followed by PCR amplification and DNA sequencing of the NS3 gene, can detect mutations associated with NS3 protease inhibitor resistance. Such mutations include the R155K mutation in HCV genotype 1a and the A156S mutation in HCV genotype 1b. These and other mutations result in resistance to some or all NS3 protease inhibitors.7,8

Question 4. What is the Q80K polymorphism?

The Q80K polymorphism is a naturally occurring amino acid substitution of glutamine to lysine at NS3 codon 80. It is found in 30% to 50% of HCV genotype 1a infected patients and in 0.5% of genotype 1b patients.6 Clinical studies have shown that when subjects with HCV genotype 1a have this polymorphism at baseline, the efficacy of simeprevir in combination with PEG and ribavirin is substantially reduced.6 Consequently, alternative therapy should be considered for such patients.6

Question 5. Is NS3 genotype testing required before prescribing an NS3 protease inhibitor-containing antiviral regimen?

NS3 genotype testing is strongly recommended for patients with HCV genotype 1a infection before prescribing simeprevir.6,9 Alternative therapy should be considered for the patient when genotype testing reveals presence of the Q80K polymorphism.6,9

Question 6. How are HCV NS3 genotype test results reported?

The HCV subtype (1a or 1b) and predicted resistance to boceprevir, telaprevir and simeprevir are reported. The mutations detected, including the Q80K polymorphism, are also reported.

Example 1  
HCV NS3 Subtype:  1a
Boceprevir Resistance: NOT PREDICTED
Telaprevir Resistance: NOT PREDICTED
Simeprevir Resistance: NOT PREDICTED
MUTATIONS DETECTED: Q80K
   
Example 2  
HCV NS3 Subtype: 1a
Boceprevir Resistance: PREDICTED
Telaprevir Resistance: PREDICTED
Simeprevir Resistance: PREDICTED
MUTATIONS DETECTED: V36M, R155K
   
Example 3  
HCV NS3 Subtype:         1b
Boceprevir Resistance:        NOT PREDICTED
Telaprevir Resistance: NOT PREDICTED
Simeprevir Resistance: NOT PREDICTED
MUTATIONS DETECTED: NONE

 

References

  1. Pawlotsky JM. Treatment of chronic hepatitis C: current and future. Curr Top Microbiol Immunol. 2013;369:321-342.
  2. Sarrazin C, Hézode C, Zeuzem S, et al. Antiviral strategies in hepatitis C virus infection. J Hepatol. 2012;56(suppl 1):S88-S100.
  3. You DM, Pockros PJ. Simeprevir for the treatment of chronic hepatitis C. Expert Opin Pharmacother. 2013;14:2581-2589.
  4. Boceprevir [package insert]. Whitehouse Station, NJ: Schering Corporation; 2011.
    http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202258lbl.pdf.
  5. Telaprevir [package insert]. Cambridge, MA: Vertex Pharmaceuticals Incorporate; 2011.
    http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/201917lbl.pdf.
  6. Simeprevir [package insert]. Titusville, NJ: Janssen Therapeutics; 2013.
    http://www.janssentherapeutics.com/shared/product/olysio/prescribing-information.pdf.
  7. Pawlotsky JM. Treatment failure and resistance with direct-acting antiviral drugs against hepatitis C virus. Hepatology. 2011;53:1742-1751.
  8. Vermehren J, Sarrazin C. The role of resistance in HCV treatment. Best Pract Res Clin Gastroenterol. 2012;26:487-503.
  9. Recommendations for Testing, Managing, and Treating Hepatitis C. AASLD and IDSA; 2013.
    http://www.hcvguidelines.org/full-report-view
This FAQ is provided for informational purposes only and is not intended as medical advice. A physician’s test selection and interpretation, diagnosis, and patient management decisions should be based on his/her education, clinical expertise, and assessment of the patient.
Document FAQS.132 Revision: 1
Version 0 effective 03/12/2014 to 07/07/2015