Hepatitis C: Direct-acting antivirals (DAAs)

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Pharmacology

Summary

Modern treatment of Hepatitis C relies on Direct-Acting Antivirals (DAAs). The DAAs are drugs that directly inhibit viral proteins, unlike older medications such as interferons that induce an immune response. The key viral proteins inhibited by DAAs are NS3/4A, NS5A, and NS5B.

The inhibitors of NS3/4A, a protease, have the suffix "previr", such as lecaprevir. Inhibitors of NS5A like lepidasvir ("asvir") rely on an unclear mechanism to inhibit viral replication and assembly. NS5B inhibitors like sofosbuvir ("buvir") block the HCV RNA-dependent RNA polymerase, ultimately preventing viral replication. All current DAA regimens use drugs from two different classes. Interferons and ribavirin are no longer recommended for the first-line treatment of HCV because of their lower cure rates and increased adverse effects. The onset of DAA treatment may be delayed by six months post-initial infection to allow for possible natural viral clearance. Furthermore, after the cessation of treatment, the effectiveness of treatment should be checked by confirming a viral level to evaluate sustained virologic response (SVR).

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FAQs

What is the typical treatment for Hepatitis C virus (HCV)?

HCV is usually treated with Direct-Acting Antivirals (DAAs). The virus may naturally clear on its own within 6 months of initial infection. If it doesn't, a DAA regimen is highly effective at clearing the virus.

What are Direct-Acting Antivirals (DAAs), and how are they classified?

Direct-Acting Antivirals (DAAs) are drugs used to treat Hepatitis C that directly target specific stages of the HCV lifecycle. They are classified based on the viral protein they inhibit - NS3/4A protease inhibitors (ending with -previr), NS5A inhibitors (ending with -asvir), and NS5B RDRP inhibitors (ending with -buvir).

What role does the NS3/4A protease play in the Hepatitis C virus, and how do NS3/4A protease inhibitors work?

NS3/4A is a protease found in HCV that is vital for its replication process. NS3/4A protease inhibitors target and block this enzyme, thereby preventing the virus from multiplying.

What were the previous Hepatitis C treatment options before DAAs, and why have they fallen out of favor?

Previously, the recommended treatment was interferon alfa with ribavirin. However, this treatment method had a lower cure rate compared to DAAs and was associated with more side effects. Therefore, it is no longer recommended for patients with Hepatitis C.

What are the common side effects of Direct-Acting Antivirals?

The common side effects of DAAs include fatigue, nausea, and headache, although many people do not experience side effects and those who do often have mild symptoms.