What are the current treatment guidelines for hepatitis C?

Current Treatment Guidelines for Hepatitis C

Direct-acting antiviral (DAA) therapy is the standard of care for all patients with chronic hepatitis C infection, with treatment regimens selected based on viral genotype, presence of cirrhosis, and prior treatment history. 1

Treatment Selection Algorithm

Step 1: Pre-treatment Testing

• Test all patients for HBV co-infection (HBsAg and anti-HBc) before starting treatment 2
• Determine HCV genotype (1-6)
• Assess for cirrhosis and its severity (compensated vs. decompensated)
• Review treatment history (naïve vs. experienced)

Step 2: Select Treatment Regimen by Genotype

Genotype 1 Infection

• Treatment-naïve without cirrhosis:

  • Ledipasvir/sofosbuvir for 12 weeks (can shorten to 8 weeks if HCV RNA <6 million IU/mL) 1
  • Elbasvir/grazoprevir for 12 weeks (check for NS5A RASs) 1
  • Glecaprevir/pibrentasvir for 8 weeks 1
  • Sofosbuvir/velpatasvir for 12 weeks 1, 2

• Treatment-naïve with compensated cirrhosis:

  • Ledipasvir/sofosbuvir for 12 weeks 1
  • Elbasvir/grazoprevir for 12 weeks 1
  • Glecaprevir/pibrentasvir for 12 weeks 1
  • Sofosbuvir/velpatasvir for 12 weeks 1, 2

• Treatment-experienced:

  • Ledipasvir/sofosbuvir + ribavirin for 12 weeks or ledipasvir/sofosbuvir for 24 weeks 1
  • Sofosbuvir/velpatasvir for 12 weeks 1, 2
  • Glecaprevir/pibrentasvir for 8-12 weeks (duration based on cirrhosis status) 1

Genotype 2 Infection

• Treatment-naïve without cirrhosis:

  • Sofosbuvir/velpatasvir for 12 weeks 1, 2
  • Glecaprevir/pibrentasvir for 8 weeks 1
  • Sofosbuvir + ribavirin for 12 weeks 1

• With compensated cirrhosis:

  • Sofosbuvir/velpatasvir for 12 weeks 1, 2
  • Glecaprevir/pibrentasvir for 12 weeks 1
  • Sofosbuvir + ribavirin for 16 weeks 1

Genotype 3 Infection

• Treatment-naïve without cirrhosis:

  • Sofosbuvir/velpatasvir for 12 weeks 1, 2
  • Glecaprevir/pibrentasvir for 8 weeks 1
  • Daclatasvir + sofosbuvir for 12 weeks 1

• With compensated cirrhosis:

  • Sofosbuvir/velpatasvir + ribavirin for 12 weeks 1
  • Glecaprevir/pibrentasvir for 12 weeks 1
  • Sofosbuvir/velpatasvir/voxilaprevir for 8 weeks 1

Genotype 4,5, or 6 Infection

• Treatment-naïve without cirrhosis:

  • Sofosbuvir/velpatasvir for 12 weeks 1, 2
  • Glecaprevir/pibrentasvir for 8 weeks 1
  • Ledipasvir/sofosbuvir for 12 weeks 1

• With compensated cirrhosis:

  • Sofosbuvir/velpatasvir for 12 weeks 1, 2
  • Glecaprevir/pibrentasvir for 12 weeks 1
  • Ledipasvir/sofosbuvir for 12 weeks 1

Step 3: Special Populations

Decompensated Cirrhosis (Child-Pugh B or C)

• Sofosbuvir/velpatasvir + ribavirin for 12 weeks 1, 2

Post-Liver Transplant

• Sofosbuvir/velpatasvir for 12 weeks 2

HCV/HIV Co-infection

• Same regimens as HCV mono-infected patients 2
• Check for drug interactions with antiretroviral therapy

Dosing Information

Sofosbuvir/velpatasvir (Preferred pangenotypic regimen)

• Adults: One tablet (400mg/100mg) once daily with or without food 2
• Pediatric patients ≥3 years: Weight-based dosing 2
  • <17kg: 150mg/37.5mg daily
  • 17kg to <30kg: 200mg/50mg daily
  • ≥30kg: 400mg/100mg daily

Ribavirin (when used in combination)

• Adults: Weight-based dosing 2
  • <75kg: 1000mg daily in divided doses
  • ≥75kg: 1200mg daily in divided doses
• Pediatric patients: Weight-based dosing 2

Treatment Efficacy and Monitoring

• Modern DAA regimens achieve sustained virological response (SVR) rates of 95-100% across all genotypes 3, 4
• Sofosbuvir/velpatasvir demonstrates 99% SVR for genotypes 1,2,4,5, and 6 3
• Sofosbuvir/velpatasvir achieves 95% SVR in genotype 3 patients 4
• For patients with advanced fibrosis/cirrhosis, SVR rates remain high at 96-99% 4

Important Considerations

• HBV reactivation risk: Monitor HCV/HBV co-infected patients for hepatitis flare or HBV reactivation during and after HCV treatment 2
• Drug interactions: Check for interactions with concomitant medications, particularly with protease inhibitor-containing regimens
• Treatment failures: For patients who fail first-line DAA therapy, sofosbuvir/velpatasvir/voxilaprevir for 12 weeks is recommended 5

Common Side Effects

• Most regimens are well-tolerated with minimal side effects 6, 3
• Common adverse events include fatigue, headache, nausea, and nasopharyngitis 6
• Ribavirin-containing regimens may cause anemia and require monitoring of hemoglobin levels

The remarkable efficacy of current DAA regimens has transformed hepatitis C from a chronic progressive disease to a curable infection, with treatment success rates exceeding 95% with 8-12 weeks of well-tolerated oral therapy.