A 28-year-old woman with genotype 1b chronic hepatitis C (HCV RNA 2.5 × 10^6 IU/mL) and no cirrhosis presents for treatment. Which of the following is the preferred first-line regimen?

Explanation

## Direct-Acting Antiviral Therapy for Chronic Hepatitis C **Key Point:** Sofosbuvir + ledipasvir (a fixed-dose combination) is the preferred first-line regimen for genotype 1 HCV infection, achieving sustained virological response (SVR) rates >95% in 12 weeks without ribavirin in treatment-naïve, non-cirrhotic patients. ### Modern HCV Treatment Paradigm | Regimen | Genotype Coverage | SVR Rate (Non-Cirrhotic) | Duration | Ribavirin Needed? | First-Line? | |---------|-------------------|--------------------------|----------|-------------------|-------------| | **Sofosbuvir + Ledipasvir** | **1, 4, 5, 6** | **>95%** | **12 weeks** | **No** | **Yes** | | Daclatasvir + Sofosbuvir | 1–6 | >95% | 12 weeks | No | Alternative | | Sofosbuvir + Ribavirin | 2, 3 | 80–90% | 12–24 weeks | Yes | No (genotype 1) | | Peginterferon + Ribavirin | 1–6 | 40–50% | 48 weeks | Yes | **Obsolete** | **High-Yield:** The era of interferon-based therapy has ended. All modern regimens are interferon-free, direct-acting antivirals (DAAs). Sofosbuvir + ledipasvir is the gold standard for genotype 1 because it is: - Pangenotypic coverage (1, 4, 5, 6) - Ribavirin-sparing in non-cirrhotic patients - 12-week fixed duration - Oral, once-daily dosing - SVR >95% in all populations ### Mechanism **Sofosbuvir** is a nucleotide polymerase inhibitor (NS5B inhibitor) with a high barrier to resistance. **Ledipasvir** is an NS5A inhibitor. The combination covers the entire HCV life cycle, achieving rapid viral clearance. ### Clinical Pearl **Warning:** Peginterferon-based regimens (48 weeks) are now considered historical. They are associated with significant side effects (flu-like symptoms, cytopenias, depression), lower SVR rates (40–50% for genotype 1), and should NOT be used in modern practice. Any question offering interferon as "first-line" is a trap. **Tip:** In NEET PG, when you see "genotype 1 HCV, treatment-naïve, non-cirrhotic," the answer is **sofosbuvir + ledipasvir for 12 weeks**. This is the most frequently tested regimen. [cite:Harrison 21e Ch 298]