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

First-Line Treatment for Hepatitis C (HCV)

The recommended first-line treatment for Hepatitis C is either sofosbuvir/velpatasvir for 12 weeks or glecaprevir/pibrentasvir for 8 weeks (12 weeks in treatment-experienced patients with cirrhosis), regardless of HCV genotype (1-6). 1

Treatment Selection Based on HCV Genotype

Genotype 1 Infection

• Without Cirrhosis:

  • Ledipasvir/sofosbuvir for 12 weeks 2, 1
  • Paritaprevir/ritonavir/ombitasvir plus dasabuvir (with ribavirin for genotype 1a, without for 1b) for 12 weeks 2
  • Sofosbuvir plus simeprevir for 12 weeks 2

• With Compensated Cirrhosis (Child-Pugh A):

  • Ledipasvir/sofosbuvir for 12 weeks 2, 1
  • Paritaprevir/ritonavir/ombitasvir plus dasabuvir (with ribavirin for 12 weeks for genotype 1b; with ribavirin for 24 weeks for genotype 1a) 2

Genotypes 2-6

• Sofosbuvir/velpatasvir for 12 weeks for all genotypes (2-6) 1, 3
• For genotype 4: Ledipasvir/sofosbuvir for 12 weeks 2, 1

Special Populations

Treatment-Experienced Patients

• Prior PEG-IFN/RBV failure:

  • Genotype 1: Ledipasvir/sofosbuvir for 12 weeks (extend to 24 weeks for cirrhosis) 2
  • Genotypes 2,4,5,6: Sofosbuvir/velpatasvir for 12 weeks 1, 3
  • Genotype 3: Sofosbuvir/velpatasvir for 16 weeks 1

• Prior protease inhibitor failure:

  • Ledipasvir/sofosbuvir for 12 weeks (without cirrhosis) or 24 weeks (with cirrhosis) 2

Patients with Cirrhosis

• Compensated Cirrhosis (Child-Pugh A):

  • Same regimens as non-cirrhotic patients, but may require longer duration (12-24 weeks) 1

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

  • Sofosbuvir/velpatasvir plus ribavirin for 12 weeks 1, 3
  • Avoid protease inhibitors (glecaprevir/pibrentasvir, paritaprevir) due to risk of toxicity 1

Ribavirin Dosing When Required

• Weight-based dosing: 1000mg for <75kg, 1200mg for ≥75kg, divided twice daily 2, 3
• For decompensated cirrhosis: Start at 600mg daily and titrate as tolerated 1

Treatment Duration

• 8 weeks: Treatment-naïve patients without cirrhosis receiving glecaprevir/pibrentasvir 1, 4
• 8 weeks: Treatment-naïve patients with HCV genotype 1 without cirrhosis and baseline HCV RNA <6 million IU/mL receiving ledipasvir/sofosbuvir 1, 5
• 12 weeks: Standard duration for most patients 2, 1
• 24 weeks: Treatment-experienced patients with cirrhosis receiving certain regimens 2

Important Monitoring Considerations

• Test all patients for HBV co-infection (HBsAg and anti-HBc) before starting treatment to prevent HBV reactivation 4, 3
• Monitor for potential drug interactions, particularly with proton pump inhibitors (which may reduce efficacy of ledipasvir/sofosbuvir) 1, 5
• Assess SVR12 (sustained virologic response at 12 weeks post-treatment) to confirm cure 1

Cautions and Contraindications

• Avoid amiodarone with sofosbuvir-containing regimens due to risk of severe bradycardia 1
• Protease inhibitors are contraindicated in decompensated cirrhosis 1
• Drug interactions with HIV antiretrovirals require careful selection of regimens in co-infected patients 1

Real-World Effectiveness

Real-world studies confirm high SVR rates (>95%) with ledipasvir/sofosbuvir regimens, consistent with clinical trials 5, 6. The 8-week regimen for eligible patients with genotype 1 has shown similar effectiveness to 12-week regimens (96% vs 98% SVR) 5.

The treatment landscape for HCV has evolved dramatically with these highly effective direct-acting antivirals, making HCV a curable infection for the vast majority of patients.