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Hepatitis C Protease Inhibitor Resistance

I was just diagnosed with hepatitis C, what medication do I need?

When you have been diagnosed with hepatitis C (or HCV), your doctor will have already completed two tests; the first which tells the doctor that you have been exposed to the hepatitis C virus and then the second, which verifies that you have the virus in your blood. At this point, the doctor will send your blood-work to a laboratory to be analyzed. This will provide your doctor with the specific genotype of your viral strain.

Different strains of hepatitis C react differently to medications, so it is important that your doctor know which strain you have in order to prescribe the best medication for you.

Why would my doctor prescribe a drug that is not interferon?

From 1991-2011, interferon was the drug most commonly associated with hepatitis C treatment. This was because it was the first drug approved to treat hepatitis C, so it was prescribed to everyone who was diagnosed with the virus. Unfortunately, there were often side effects associated with interferon, but for a long time, there was no alternative, so interferon continued to be regularly prescribed for patients with hepatitis C.

In the decades since interferon’s drug approval, however, many new drugs have been approved by the FDA, and many new and more specific tests have been perfected to understand more about the different genotypes of the viral strains of HCV. This means that there is rarely, if ever, a need to prescribe interferon anymore.

For example: A long time ago, bleach was commonly used for cleaning a home. It was used everywhere and did a decent enough job. However, in the time since, there have been new cleaning products invented. We now have a glass cleaner for mirrors and glass, a tub and tile cleaner for shower areas, and even floor cleaners that are different, based on whether you have vinyl floors or hardwood floors. Moreover, we have learned that bleach can cause damage to carpets, rugs, and other areas of the house.

Think of interferon as bleach and the newer medications as the newer types of cleaning products. Now, when you need to clean your home, you can choose the specific solutions to clean the specific problem areas in your home without causing unnecessary damage. Similarly, when your doctor needs to treat the hepatitis C virus in your body, you can now be prescribed a medication that is both specific to your needs and that is as least likely as possible to cause damage through side effects.

This is why you are unlikely to be prescribed interferon. It is also why you and someone else you know who has been diagnosed with HCV may be on different medication plans.

What is hepatitis C protease inhibitor resistance?

The goal of hepatitis C medication is to find the specific part of the virus that replicates (or makes more of the virus) and prevent it from doing so, thus stopping the virus from making more of itself. By choosing medication specific to your virus’ genome, it increases the likelihood of finding a perfect match between the part of the virus that replicates and the drug being used. In some cases, though, there is an enzyme in the virus that is able to mutate slightly, which makes the medication less successful.

For example: Think of hepatitis C as a hole. Different holes have different shapes, just as there are different genomes of the hepatitis C virus. Your blood-work will allow your doctor to know which genome you have, just like you could see a hole and know what shape it is. The goal is to find the right fit for your virus’ genome or to find the right shape for the hole you see. In the best case scenario, the drug chosen works with the genome strain, and it is successful, just as the best case to plug the hole would be to choose a round block to plug a round hole.

HCV protease inhibitor resistance occurs when the enzyme in the virus alters itself slightly, which makes the medication not work as effectively or at all. This would be like the round hole suddenly changing and becoming an oval or a heart shape. If it is an oval, the round block you used might still fit somewhat into the oval-shaped hole, but it would not be a perfect fit. If the hole becomes heart-shaped, the round block you used will no longer fit at all.

At this point, the doctor would alter the medication being used, just as you would recognize a change in the hole’s shape and choose a different and more appropriate block to fit the new hole shape.

Should I be worried about hepatitis C protease inhibitor resistance?

There is no reason to be worried! Your doctor can work with you to discuss any concerns you may have – all of which are totally normal. Never feel badly about discussing your questions or fears with your doctor at any time during your diagnostic tests or treatment. As your doctor is aware, HCV protease inhibitor resistance is very common. Knowing this, your doctor will be monitoring you via blood-work and possibly through other tests to make sure your medication regimen is working. If your body is showing signs of resistance, your doctor is likely to discuss this with you, as well as working with you to choose an alternative drug therapy that may be better suited for your needs.1-7

  1. Halfon, P. & Locarnini, S. (2011). Hepatitis C virus resistance to protease inhibitors. Journal Of Hepatology, 55(1), 192-206.
  2. Monitoring Patients Who Are Starting Hepatitis C Treatment, Are On Treatment, Or Have Completed Therapy | Recommendations for Testing, Managing, and Treating Hepatitis C. (2016). Retrieved 25 June 2016, from
  3. Romono, K., Ali, A., Aydin, C., Soumana, D., Özen, A., & Deveau, L. et al. (2012). The Molecular Basis of Drug Resistance against Hepatitis C Virus NS3/4A Protease Inhibitors. Plos Pathog, 8(7), e1002832.
  4. Rong, L., Dahari, H., Ribeiro, R., & Perelson, A. (2010). Rapid Emergence of Protease Inhibitor Resistance in Hepatitis C Virus. Science Translational Medicine, 2(30), 30ra32-30ra32.
  5. Schneider, M. & Sarrazin, C. (2014). Antiviral therapy of hepatitis C in 2014: Do we need resistance testing?. Antiviral Research, 105, 64-71.
  6. Shang, L., Lin, K., & Yin, Z. (2016). Resistance mutations against HCV protease inhibitors and antiviral drug design. - PubMed - NCBI. Retrieved 25 June 2016, from
  7. Wyles, D. (2013). Antiviral Resistance and the Future Landscape of Hepatitis C Virus Infection Therapy. Journal Of Infectious Diseases, 207(suppl 1), S33-S39.