First-Line Treatment for Hepatitis C Management
The recommended first-line treatment for Hepatitis C is either the fixed-dose combination of 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, 2
Treatment Recommendations Based on Patient Characteristics
Treatment-Naïve Patients
Without Cirrhosis:
Genotypes 1,2,4,5,6:
- Sofosbuvir/velpatasvir for 12 weeks OR
- Glecaprevir/pibrentasvir for 8 weeks 1
Genotype 3:
- Sofosbuvir/velpatasvir for 12 weeks OR
- Glecaprevir/pibrentasvir for 8 weeks 1
With Compensated Cirrhosis (Child-Pugh A):
Genotypes 1,2,4,5,6:
- Sofosbuvir/velpatasvir for 12 weeks OR
- Glecaprevir/pibrentasvir for 8 weeks 1
Genotype 3:
- Sofosbuvir/velpatasvir with ribavirin for 12 weeks OR
- Sofosbuvir/velpatasvir/voxilaprevir for 12 weeks OR
- Glecaprevir/pibrentasvir for 12 weeks (can be shortened to 8 weeks, but more data needed) 1
Treatment-Experienced Patients
Without Cirrhosis:
Genotypes 1,2,4,5,6:
- Sofosbuvir/velpatasvir for 12 weeks OR
- Glecaprevir/pibrentasvir for 8 weeks (genotype 1) or 12 weeks (genotypes 2,4,5,6) 1
Genotype 3:
- Sofosbuvir/velpatasvir for 12 weeks OR
- Glecaprevir/pibrentasvir for 12 weeks 1
With Compensated Cirrhosis (Child-Pugh A):
Genotypes 1,2,4,5,6:
- Sofosbuvir/velpatasvir for 12 weeks OR
- Glecaprevir/pibrentasvir for 12 weeks 1
Genotype 3:
- Sofosbuvir/velpatasvir with ribavirin for 12 weeks OR
- Sofosbuvir/velpatasvir/voxilaprevir for 12 weeks OR
- Glecaprevir/pibrentasvir for 16 weeks 1
Decompensated Cirrhosis (Child-Pugh B or C):
- Sofosbuvir/velpatasvir with ribavirin for 12 weeks 2, 3
- Important: Protease inhibitors (including glecaprevir) should be avoided in decompensated cirrhosis due to risk of toxicity 2
Special Considerations
Resistance Testing
- For genotype 3 patients with compensated cirrhosis, NS5A resistance testing for Y93H mutation is recommended:
- If Y93H is present: Use sofosbuvir/velpatasvir plus ribavirin OR sofosbuvir/velpatasvir/voxilaprevir for 12 weeks
- If Y93H is absent: Sofosbuvir/velpatasvir alone for 12 weeks is sufficient 1
HBV Coinfection
- Critical safety warning: Test all patients for HBV (HBsAg and anti-HBc) before starting treatment 3, 4
- HBV reactivation has been reported during DAA therapy, potentially leading to fulminant hepatitis and death
- Monitor HBV/HCV coinfected patients for hepatitis flare during and after treatment 3, 4
Ribavirin Dosing
- Weight-based dosing: 1,000 mg/day for patients <75 kg and 1,200 mg/day for patients ≥75 kg, divided twice daily 3
- For decompensated cirrhosis: Consider starting at 600 mg daily and titrate as tolerated 2
Drug Interactions
- Avoid coadministration of amiodarone with sofosbuvir/velpatasvir (risk of serious bradycardia) 2
- Caution with proton pump inhibitors and certain antiretrovirals 2
- First-generation anticonvulsants (carbamazepine, phenytoin, phenobarbital) may reduce DAA levels 5
Treatment Outcomes
Both recommended regimens achieve sustained virologic response (SVR) rates >95% across all genotypes 2, making them highly effective first-line options for hepatitis C management.