What is the recommended first-line treatment for Hepatitis C (HCV) management?

First-Line Treatment for Hepatitis C Virus (HCV) Infection

Sofosbuvir/velpatasvir (400mg/100mg) once daily for 12 weeks is the recommended first-line treatment for hepatitis C virus (HCV) infection, regardless of HCV genotype (1-6), prior treatment experience, or compensated cirrhosis status. 1

Treatment Selection Based on Current Guidelines

The management of HCV has evolved dramatically with the development of direct-acting antivirals (DAAs), which have replaced interferon-based regimens as the standard of care.

Preferred First-Line Regimen:

• Sofosbuvir/velpatasvir (400mg/100mg) once daily for 12 weeks
  • FDA-approved for all HCV genotypes (1-6) 2
  • High sustained virologic response (SVR) rates of >95%
  • Well-tolerated with minimal side effects
  • Can be used in patients with or without compensated cirrhosis

Alternative First-Line Options:

For specific genotypes when sofosbuvir/velpatasvir is not available:

• Genotype 1:

  • Ledipasvir/sofosbuvir (90mg/400mg) once daily for 12 weeks
  • Glecaprevir/pibrentasvir (300mg/120mg) once daily for 8 weeks 3

• Genotypes 2-6:

  • Glecaprevir/pibrentasvir (300mg/120mg) once daily for 8 weeks (no cirrhosis) or 12 weeks (compensated cirrhosis) 3

Treatment Duration

Treatment duration varies based on:

1. Cirrhosis status:

   • No cirrhosis: 8-12 weeks
   • Compensated cirrhosis: 12 weeks
   • Decompensated cirrhosis: 12 weeks (with ribavirin)

2. Prior treatment experience:

   • Treatment-naïve: Standard duration
   • Treatment-experienced: May require extended duration (12-16 weeks)

Special Considerations

Decompensated Cirrhosis

For patients with decompensated cirrhosis (Child-Pugh B or C), sofosbuvir/velpatasvir plus ribavirin for 12 weeks is recommended 1. Protease inhibitors (including glecaprevir/pibrentasvir) are contraindicated in decompensated cirrhosis due to risk of toxicity.

Ribavirin Addition

Ribavirin should be added in specific situations:

• Decompensated cirrhosis
• Post-transplant patients
• Some treatment-experienced patients with cirrhosis

Dosing: 1,000 mg for patients <75 kg and 1,200 mg for those ≥75 kg, divided and administered twice daily 2.

Pre-Treatment Testing

Before initiating treatment:

1. Confirm active HCV infection with HCV RNA testing
2. Determine HCV genotype
3. Assess liver fibrosis stage
4. Screen for hepatitis B co-infection (HBsAg and anti-HBc) 2, 3
5. Evaluate for potential drug interactions

Monitoring During Treatment

• No routine HCV RNA monitoring required during treatment
• Monitor for adverse effects (headache, fatigue, nausea)
• HCV RNA testing at 12 weeks post-treatment to confirm SVR (cure)
• For patients with cirrhosis, closer monitoring for signs of decompensation

Common Pitfalls to Avoid

1. Failing to screen for HBV co-infection: HBV reactivation can occur during DAA therapy, potentially resulting in fulminant hepatitis 2, 3

2. Drug interactions: Particularly with:

   • Proton pump inhibitors (with ledipasvir/sofosbuvir)
   • Amiodarone (with sofosbuvir-containing regimens)
   • Antiretrovirals in HIV co-infected patients

3. Inadequate assessment of liver fibrosis: Proper staging is vital for determining treatment urgency and duration 4

4. Overlooking resistance testing: For certain genotypes (particularly 1a), resistance testing may guide treatment selection in specific scenarios

The evolution from interferon-based regimens to all-oral DAA combinations has transformed HCV from a difficult-to-treat chronic infection to a curable disease with short-duration, well-tolerated therapy. With current first-line regimens, SVR rates exceed 95% for most patient populations, effectively representing a cure for HCV infection.