## First-Line Treatment of Chronic Hepatitis C ### Current Standard of Care **Key Point:** Direct-acting antivirals (DAAs) are now the standard of care for all genotypes of chronic hepatitis C, replacing interferon-based regimens. **High-Yield:** Sofosbuvir + Velpatasvir is a pan-genotypic, all-oral, fixed-dose combination that achieves sustained virological response (SVR12) rates >95% across all HCV genotypes (1–6) with minimal side effects and no need for ribavirin in most cases [cite:Harrison 21e Ch 360]. ### Why DAAs Are Superior | Feature | DAAs (Sofosbuvir + Velpatasvir) | Interferon + Ribavirin | |---------|--------------------------------|------------------------| | SVR rate | >95% | 50–70% | | Duration | 12 weeks | 24–48 weeks | | Side effects | Minimal | Flu-like, anemia, depression | | Genotype coverage | Pan-genotypic | Genotype-dependent | | Contraindications | Minimal | Many (pregnancy, cardiac disease) | | Renal impairment | Caution (eGFR <30) | Relative contraindication | ### Mechanism of DAAs 1. **Sofosbuvir** — Nucleotide analog NS5B polymerase inhibitor (non-structural protein 5B inhibitor); blocks viral RNA replication. 2. **Velpatasvir** — NS5A inhibitor; prevents viral assembly and secretion. **Clinical Pearl:** The combination achieves rapid viral clearance (HCV RNA becomes undetectable by week 2–4 in most patients), with excellent tolerability even in cirrhotic patients and those with renal impairment (though dose adjustment may be needed for eGFR <30 mL/min). ### Treatment Duration - **Non-cirrhotic, treatment-naïve:** 12 weeks - **Cirrhotic or treatment-experienced:** 12 weeks (sofosbuvir + velpatasvir ± voxilaprevir) - **Decompensated cirrhosis:** Requires specialist input; DAAs are still preferred but may need additional agents. **Key Point:** SVR12 (sustained virological response at 12 weeks post-treatment) is the gold standard endpoint and predicts cure in >99% of cases.
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