Direct-Acting Antivirals (Hepatitis C & B)

Direct-Acting Antivirals (Hepatitis C & B)

1. Definition & scope

• Direct-acting antivirals (DAAs) are small-molecule oral drugs that directly target specific viral non-structural (NS) proteins essential for hepatitis C virus (HCV) replication, in contrast to the indirect/immunomodulatory action of interferons (G&G 14e Ch.63, pp.1234; KDT 8e Ch.59, p.858).
• The term "DAA" is used almost exclusively for HCV; HBV is treated with nucleoside/nucleotide analogues plus pegIFN-α, which are not conventionally labelled "DAAs" but act directly on HBV polymerase — this topic covers both (G&G 14e Ch.63, pp.1228, 1234).
• Two fundamentally different therapeutic paradigms despite both being chronic hepatotropic viral infections (G&G 14e Ch.63, p.1227):
  • HCV — a positive-sense RNA flavivirus, replicates entirely in cytoplasm, does not integrate or establish latency, and is curable; cure = sustained virologic response (SVR) (G&G 14e Ch.63, pp.1227, 1234; KDT 8e Ch.59, p.856).
  • HBV — a partially double-stranded DNA hepadnavirus, forms nuclear cccDNA that current drugs cannot eliminate, so a complete cure is not currently possible; treatment suppresses replication lifelong (G&G 14e Ch.63, pp.1227–8; KDT 8e Ch.59, p.854).
• Hepatitis A and E (faecal-oral, usually self-limiting) have no antiviral therapy; hepatitis D (defective, needs HBV) has limited options (pegIFN-α, bulevirtide) (G&G 14e Ch.63, p.1227).
• Key distinctions between HBV and HCV (G&G 14e Ch.63, p.1227):
  • HBV is vaccine-preventable; HCV has no vaccine (due to extreme genetic heterogeneity).
  • HCV can be cured; HBV current therapy is not curative.