What is the recommended treatment for Hepatitis C Virus (HCV) infection?

Recommended Treatment for Hepatitis C Virus (HCV) Infection

The recommended first-line treatment for hepatitis C virus (HCV) infection is a 12-week course of direct-acting antiviral (DAA) therapy with sofosbuvir/velpatasvir (400mg/100mg) taken once daily, regardless of HCV genotype (1-6), prior treatment experience, or compensated cirrhosis status. 1

Treatment Selection Based on HCV Genotype

For All Genotypes (Pangenotypic Approach)

• Sofosbuvir/velpatasvir (400mg/100mg) once daily for 12 weeks
  • Achieves SVR rates of 97-100% across all genotypes
  • First-line option for most patients due to high efficacy and good tolerability

Genotype-Specific Options

• Genotype 1:

  • Ledipasvir/sofosbuvir (90mg/400mg) once daily for 12 weeks (96-99% SVR) 2
  • Consider 8 weeks of ledipasvir/sofosbuvir in treatment-naïve patients without cirrhosis who have baseline HCV RNA <6 million IU/mL 2, 3
  • Alternative options: sofosbuvir/simeprevir or paritaprevir/ritonavir/ombitasvir plus dasabuvir 1

• Genotypes 2 and 3:

  • Sofosbuvir/velpatasvir for 12 weeks
  • For genotype 2: Consider sofosbuvir plus ribavirin for 12 weeks if other options unavailable 4
  • For genotype 3: Consider sofosbuvir/velpatasvir/voxilaprevir or glecaprevir/pibrentasvir, especially in treatment-experienced patients 1

• Genotypes 4,5, and 6:

  • Sofosbuvir/velpatasvir or ledipasvir/sofosbuvir for 12 weeks 4, 1

Special Populations

Cirrhotic Patients

• Compensated cirrhosis (Child-Pugh A):

  • Standard DAA regimens as above
  • Consider extending therapy to 24 weeks in treatment-experienced patients with genotype 1 and cirrhosis 4

• Decompensated cirrhosis (Child-Pugh B or C):

  • Sofosbuvir/velpatasvir + ribavirin for 12 weeks
  • Ledipasvir/sofosbuvir + ribavirin for 12 weeks 2
  • Avoid protease inhibitors (including glecaprevir/pibrentasvir) due to risk of toxicity 1

Post-Liver Transplant

• Sofosbuvir/ledipasvir + ribavirin for 12 weeks achieves SVR rates of 96-98% in patients without cirrhosis or with compensated cirrhosis 4, 5
• For severe recurrence (fibrosing cholestatic hepatitis), sofosbuvir-based regimens have shown excellent efficacy 4

Treatment-Experienced Patients

• Prior failure with peginterferon/ribavirin:
  • Standard DAA regimens as per genotype
• Prior failure with DAA regimens:
  • Sofosbuvir/velpatasvir/voxilaprevir for 12 weeks
  • Glecaprevir/pibrentasvir for 16 weeks 1

Ribavirin Considerations

• Add ribavirin (weight-based dosing: 1000mg for <75kg, 1200mg for ≥75kg) in:
  • Decompensated cirrhosis
  • Post-transplant patients
  • Some treatment-experienced patients with cirrhosis 4, 1
• Starting dose of 600mg daily in decompensated cirrhosis, titrate as tolerated 4

Monitoring

• HCV RNA testing at 12 weeks post-treatment to confirm SVR12
• No routine HCV RNA monitoring required during treatment
• Monitor for adverse effects (headache, fatigue, nausea)
• For patients with cirrhosis, monitor for signs of decompensation

Important Precautions

• Test all patients for HBV co-infection (HBsAg, anti-HBc) before starting therapy 2
• Monitor for HBV reactivation in co-infected patients
• Check for drug interactions, particularly with:
  • Proton pump inhibitors (may reduce efficacy of ledipasvir) 3
  • Amiodarone (contraindicated with sofosbuvir due to risk of bradycardia) 1
  • HIV antiretrovirals in co-infected patients

Treatment Duration Considerations

Mathematical modeling suggests that many patients may achieve viral cure before the standard 12-week treatment course, with 43% potentially cured by week 6 and 73% by week 8 6. However, until more prospective data supports shortened regimens, the standard 12-week course remains recommended for most patients to ensure optimal SVR rates.