hepatitis C virus Treatment indications

(<www.hcvguidelines.org>) (Lancet 2019;393:1453; Hepatology 2020;71:686)

Acute: if no spont. clearance at ↣ 12-16 wk, can Rx w/ same regimens for chronic HCV

Chronic: ↓ HCC & mortality. Recommended for all except if ↓ life expectancy. Here is the information as a Markdown outline:

• Potency

  • Protease inhibitors: High (varies by HCV genotype)
  • Nucleos(t)ide polymerase inhibitors: Moderate-to-high (consistent across HCV genotypes and subtypes)
  • Non-nucleoside polymerase inhibitors: Varies by HCV genotype
  • NS5A inhibitors: High (against multiple HCV genotypes)

• Barrier to resistance

  • Protease inhibitors: Low (1a <1b)
  • Nucleos(t)ide polymerase inhibitors: High (1a = 1b)
  • Non-nucleoside polymerase inhibitors: Very low (1a <1b)
  • NS5A inhibitors: Low (1a <1b)

• Potential for drug interactions

  • Protease inhibitors: High
  • Nucleos(t)ide polymerase inhibitors: Low
  • Non-nucleoside polymerase inhibitors: Variable
  • NS5A inhibitors: Low-to-moderate

• Toxicity

  • Protease inhibitors: Rash, anemia, ↑ bilirubin
  • Nucleos(t)ide polymerase inhibitors: Mitochondrial toxicity, interactions with HIV antiretrovirals (nucleoside reverse transcriptase inhibitors) and ribavirin*
  • Non-nucleoside polymerase inhibitors: Variable
  • NS5A inhibitors: Variable

• Dosing

  • Protease inhibitors: daily to three times daily
  • Nucleos(t)ide polymerase inhibitors: daily to twice daily
  • Non-nucleoside polymerase inhibitors: daily to three times daily
  • NS5A inhibitors: daily

• Comments

  • Protease inhibitors: Later generation protease inhibitors are expected to have higher barriers to resistance and be pan-genotype
  • Nucleos(t)ide polymerase inhibitors: Single target for binding at the active site
  • Non-nucleoside polymerase inhibitors: Many targets for binding at allosteric sites