Recommended Treatment Regimens for Hepatitis C Virus (HCV)
The fixed-dose combination of sofosbuvir (400 mg) and velpatasvir (100 mg) taken once daily for 12 weeks without ribavirin is the recommended first-line treatment for all HCV genotypes (1-6), regardless of cirrhosis status or treatment experience. 1
Genotype-Specific Treatment Options
Genotype 1
- First choice: Sofosbuvir/velpatasvir for 12 weeks without ribavirin 2
- Alternative options:
- Sofosbuvir/ledipasvir for 12 weeks without ribavirin (treatment-naïve) 2
- Treatment can be shortened to 8 weeks in treatment-naïve patients without cirrhosis if their baseline HCV RNA level is below 6 million IU/ml 2, 3, 4
- For treatment-experienced patients with genotype 1a with or without compensated cirrhosis: Sofosbuvir/ledipasvir for 12 weeks with ribavirin 2
Genotype 2
- First choice: Sofosbuvir/velpatasvir for 12 weeks without ribavirin 2
- Alternative: Sofosbuvir and daclatasvir for 12 weeks without ribavirin 2
Genotype 3
- First choice: Sofosbuvir/velpatasvir for 12 weeks without ribavirin (treatment-naïve without cirrhosis) 2
- For treatment-experienced patients or those with cirrhosis: Sofosbuvir/velpatasvir for 12 weeks with ribavirin 2
Genotype 4,5, or 6
- First choice: Sofosbuvir/velpatasvir for 12 weeks without ribavirin 2
- Alternative: Sofosbuvir/ledipasvir for 12 weeks without ribavirin 2
Special Populations
Patients with Compensated Cirrhosis (Child-Pugh A)
- Generally can receive the same regimens as non-cirrhotic patients 1
- For genotype 1a treatment-experienced patients: Consider extending therapy duration or adding ribavirin 2
Patients with Decompensated Cirrhosis (Child-Pugh B or C)
- Sofosbuvir/velpatasvir plus weight-based ribavirin for 12 weeks 1
- Sofosbuvir/ledipasvir plus ribavirin for 12 weeks for genotype 1 5
HCV/HIV Co-infection
- Same regimens as HCV mono-infected patients 2, 5
- Check for potential drug interactions with antiretroviral medications 1
Important Considerations
HBV Reactivation Risk
- Test all patients for evidence of current or prior HBV infection (HBsAg and anti-HBc) before starting HCV treatment 5, 6
- HBV reactivation has been reported during or after HCV treatment with direct-acting antivirals, which can lead to fulminant hepatitis, hepatic failure, and death 5
Drug Interactions
- Avoid coadministration of amiodarone with sofosbuvir-containing regimens due to risk of serious symptomatic bradycardia 1, 6
- Check for interactions with proton pump inhibitors, especially with ledipasvir/sofosbuvir 1, 3
- P-glycoprotein inducers (e.g., rifampin, St. John's wort) may alter sofosbuvir concentrations 6
Monitoring
- SVR12 testing (HCV RNA) should be performed 12 weeks after completion of therapy 1
- Monitor for adverse effects such as fatigue, headache, nausea, and insomnia 7, 8
- For patients with cirrhosis, closer monitoring is required with the possibility of stopping therapy if there is evidence of worsening decompensation 1
Treatment Failure
- Patients who failed previous pegylated IFN-α and ribavirin treatment should be treated according to current genotype-specific recommendations 2
- For patients who failed a DAA-containing regimen, retreatment with an IFN-free regimen for 12-24 weeks with weight-based ribavirin is recommended, with duration based on fibrosis stage 2
The landscape of HCV treatment has dramatically improved with the introduction of direct-acting antivirals, offering high cure rates (>95%) with shorter treatment durations and fewer side effects compared to older interferon-based therapies.