What is the recommended treatment regimen for Hepatitis C?

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Last updated: September 2, 2025View editorial policy

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Recommended Treatment for Hepatitis C

The recommended first-line treatment for hepatitis C is sofosbuvir/velpatasvir for 12 weeks, which is effective across all HCV genotypes (1-6) regardless of cirrhosis status or treatment experience. 1

Treatment Regimens Based on Patient Characteristics

For Non-Cirrhotic Patients:

  • Treatment-naïve and treatment-experienced patients with genotypes 1a, 1b, 2,4,5, or 6:

    • Sofosbuvir/velpatasvir for 12 weeks 1
    • Alternative: Glecaprevir/pibrentasvir for 8 weeks 1
  • Treatment-naïve patients with genotype 3:

    • Sofosbuvir/velpatasvir for 12 weeks 1
    • Alternative: Glecaprevir/pibrentasvir for 8 weeks 1
  • Treatment-experienced patients with genotype 3:

    • Sofosbuvir/velpatasvir for 12 weeks 1
    • Alternative: Glecaprevir/pibrentasvir for 12 weeks 1

For Compensated Cirrhosis (Child-Pugh A):

  • Treatment-naïve patients with genotypes 1a, 1b, 2,4,5, or 6:

    • Sofosbuvir/velpatasvir for 12 weeks 1
    • Alternative: Glecaprevir/pibrentasvir for 8 weeks 1
  • Treatment-experienced patients with genotypes 1a, 1b, 2,4,5, or 6:

    • Sofosbuvir/velpatasvir for 12 weeks 1
    • Alternative: Glecaprevir/pibrentasvir for 12 weeks 1
  • Treatment-naïve patients with genotype 3:

    • Sofosbuvir/velpatasvir with ribavirin for 12 weeks 1
    • Alternative: Sofosbuvir/velpatasvir/voxilaprevir for 12 weeks 1
    • Alternative: Glecaprevir/pibrentasvir for 12 weeks 1
  • Treatment-experienced patients with genotype 3:

    • Sofosbuvir/velpatasvir with ribavirin for 12 weeks 1
    • Alternative: Sofosbuvir/velpatasvir/voxilaprevir for 12 weeks 1
    • Alternative: Glecaprevir/pibrentasvir for 16 weeks 1

For Decompensated Cirrhosis (Child-Pugh B or C):

  • All genotypes:
    • Sofosbuvir/velpatasvir with weight-based ribavirin for 12 weeks 2

Special Considerations

NS5A Resistance Testing

  • For genotype 3 patients with compensated cirrhosis, if NS5A resistance testing is performed:
    • Patients with Y93H mutation: Use sofosbuvir/velpatasvir plus ribavirin for 12 weeks or sofosbuvir/velpatasvir/voxilaprevir for 12 weeks 1
    • Patients without Y93H mutation: Use sofosbuvir/velpatasvir alone for 12 weeks 1

Ribavirin Dosing

  • Weight-based ribavirin dosing: 1,000 mg daily for patients <75 kg and 1,200 mg daily for patients ≥75 kg, divided into two doses 2
  • For patients with contraindications to ribavirin: Consider extending treatment duration to 24 weeks 1

HBV Co-infection Warning

  • Test all patients for evidence of current or prior HBV infection (HBsAg and anti-HBc) before starting HCV treatment 2
  • HBV reactivation has been reported in HCV/HBV co-infected patients during or after DAA therapy, with some cases resulting in fulminant hepatitis, hepatic failure, and death 2
  • Monitor co-infected patients for hepatitis flare or HBV reactivation during and after treatment 2

Treatment Efficacy

Real-world evidence from a study of 5,552 patients treated with sofosbuvir/velpatasvir showed an overall SVR rate of 98.9%, including 98.3% in genotype 3 patients and 97.9% in those with compensated cirrhosis 3. This confirms the high effectiveness of this regimen across diverse patient populations.

Common Side Effects

The most common adverse events with sofosbuvir/velpatasvir are headache, fatigue, and nausea 4. The regimen is generally well-tolerated with low rates of serious adverse events 5.

Key Pitfalls to Avoid

  1. Failing to test for HBV co-infection before starting treatment
  2. Not considering drug interactions, particularly with proton pump inhibitors and amiodarone
  3. Inadequate monitoring of patients with cirrhosis
  4. Not recognizing the need for ribavirin in specific populations, especially those with decompensated cirrhosis or certain resistance patterns
  5. Losing patients to follow-up (a significant cause of non-SVR in real-world settings) 3

The pangenotypic nature of sofosbuvir/velpatasvir makes it an ideal first-line choice for hepatitis C treatment, simplifying the approach to therapy while maintaining excellent cure rates across all patient populations.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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