What is the recommended treatment regimen for Hepatitis C?

Recommended Treatment for Hepatitis C

The recommended first-line treatment for chronic hepatitis C is a pangenotypic direct-acting antiviral (DAA) regimen consisting of either sofosbuvir/velpatasvir for 12 weeks or glecaprevir/pibrentasvir for 8-12 weeks, depending on cirrhosis status and treatment history. 1, 2

First-Line Treatment Options

• Sofosbuvir/velpatasvir (400mg/100mg) once daily for 12 weeks is effective for all HCV genotypes (1-6) in patients without cirrhosis or with compensated cirrhosis (Child-Pugh A) 1, 3
• Glecaprevir/pibrentasvir for 8 weeks is recommended for patients without cirrhosis, and for 12 weeks in those with compensated cirrhosis 1, 2
• For patients with decompensated cirrhosis (Child-Pugh B or C), sofosbuvir/velpatasvir plus ribavirin for 12 weeks is the recommended regimen 3

Treatment Based on HCV Genotype

While pangenotypic regimens are preferred, genotype-specific options may be considered when genotyping is available:

• Genotype 1a:

  • Without cirrhosis: Ledipasvir (90mg)/sofosbuvir (400mg) daily for 12 weeks or sofosbuvir plus simeprevir for 12 weeks (if Q80K variant negative) 1
  • Treatment duration can be shortened to 8 weeks in treatment-naïve patients with HCV RNA <6 million IU/ml without cirrhosis 4, 5

• Genotype 1b:

  • Ledipasvir/sofosbuvir daily for 12 weeks or paritaprevir/ritonavir/ombitasvir plus dasabuvir for 12 weeks 1
  • High SVR rates (approximately 96%) have been demonstrated with ledipasvir/sofosbuvir in clinical trials 6

• Genotype 2:

  • Sofosbuvir/velpatasvir for 12 weeks without ribavirin 1

• Genotype 3:

  • Treatment-naïve without cirrhosis: Sofosbuvir/velpatasvir for 12 weeks 1
  • Treatment-experienced or with cirrhosis: Sofosbuvir/velpatasvir plus ribavirin for 12 weeks 1

• Genotypes 4,5, and 6:

  • Sofosbuvir/velpatasvir for 12 weeks without ribavirin 1, 6

Special Populations

• HIV/HCV co-infection:

  • The same HCV treatment regimens are recommended as in patients without HIV infection, with dose adjustments needed for potential drug interactions with antiretroviral medications 1, 2
  • High SVR rates have been observed in HIV/HCV co-infected patients treated with ledipasvir/sofosbuvir for 12 weeks 4

• Liver transplant recipients:

  • Sofosbuvir/velpatasvir once daily for 12 weeks may be considered 1
  • For post-liver transplant HCV recurrence, ledipasvir/sofosbuvir has shown efficacy 5

• Pediatric patients (≥3 years):

  • Weight-based dosing of sofosbuvir/velpatasvir is recommended 3
  • For patients ≥30kg: One sofosbuvir/velpatasvir 400mg/100mg tablet once daily 3
  • For patients 17-<30kg: One sofosbuvir/velpatasvir 200mg/50mg tablet once daily 3
  • For patients <17kg: One 150mg/37.5mg packet of sofosbuvir/velpatasvir oral pellets once daily 3

• Acute HCV infection:

  • Sofosbuvir/velpatasvir for 8 weeks has shown 100% SVR12 in adherent patients with acute HCV monoinfection 7

Important Pre-Treatment Testing

• Test all patients for evidence of current or prior HBV infection by measuring hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) before initiating HCV treatment 3
• HBV reactivation has been reported in HCV/HBV co-infected patients undergoing DAA therapy without concurrent HBV antiviral therapy 3

Monitoring During and After Treatment

• Monitor HCV RNA levels at baseline, during treatment, at the end of treatment, and 12 weeks after completion to assess sustained virologic response (SVR) 1
• For patients with cirrhosis, continue monitoring for hepatocellular carcinoma with ultrasound every 6 months, even after achieving SVR 1, 2
• For HCV/HBV co-infected patients, monitor for hepatitis flare or HBV reactivation during and after HCV treatment 3

Common Pitfalls and Caveats

• Carefully evaluate drug-drug interactions before initiating DAA therapy, particularly in patients on multiple medications 1
• For patients with HCV genotype 1a who have the NS3 Q80K polymorphism, avoid sofosbuvir and simeprevir due to lower SVR rates 1
• The efficacy of sofosbuvir/velpatasvir has not been established in patients who have previously failed treatment with other regimens that include an NS5A inhibitor 3
• When ribavirin is added to the regimen, dose adjustments may be needed based on hemoglobin levels and creatinine clearance 3