Recommended Treatment for Chronic Hepatitis C
Direct-acting antiviral (DAA) therapy is the standard of care for all patients with chronic hepatitis C, with specific regimens selected based on viral genotype, presence of cirrhosis, and prior treatment history. 1
Treatment Selection Algorithm
Step 1: Determine HCV Genotype and Liver Status
- Identify HCV genotype (1-6)
- Assess for presence of cirrhosis (no cirrhosis, compensated cirrhosis, or decompensated cirrhosis)
- Evaluate treatment history (treatment-naïve or treatment-experienced)
Step 2: Select Appropriate DAA Regimen
For Patients Without Cirrhosis:
- Genotype 1-6 (pangenotypic): Sofosbuvir/velpatasvir for 12 weeks 2, 3
- Genotype 1-6: Glecaprevir/pibrentasvir for 8 weeks 2, 1
- Genotype 1: Ledipasvir/sofosbuvir for 12 weeks (can shorten to 8 weeks if HCV RNA <6 million IU/mL) 2, 1
- Genotype 1: Elbasvir/grazoprevir for 12 weeks 2, 1
For Patients With Compensated Cirrhosis (Child-Pugh A):
- Genotype 1-6: Sofosbuvir/velpatasvir for 12 weeks 2, 3
- Genotype 1-6: Glecaprevir/pibrentasvir for 12 weeks 2, 1
- Genotype 1: Ledipasvir/sofosbuvir for 12 weeks 2, 1
- Genotype 1: Elbasvir/grazoprevir for 12 weeks 2
For Patients With Decompensated Cirrhosis (Child-Pugh B or C):
- Genotype 1-6: Sofosbuvir/velpatasvir plus ribavirin for 12 weeks 2, 3
- Ribavirin dosing: 1,000 mg/day for patients <75 kg and 1,200 mg/day for those ≥75 kg, divided twice daily 3
Step 3: Special Populations Considerations
Treatment-Experienced Patients:
- Failed prior DAA therapy: Sofosbuvir/velpatasvir/voxilaprevir for 12 weeks 2, 1
- Failed interferon-based therapy: Follow recommendations based on genotype and cirrhosis status above 2
HCV/HIV Co-infection:
- Same regimens as HCV mono-infection with attention to drug interactions 3
Important Clinical Considerations
Monitoring Requirements
- Before treatment: Test for HBV co-infection (HBsAg and anti-HBc) 1, 3
- During treatment: Monitor for HBV reactivation in co-infected patients 3
- For ribavirin-containing regimens: Monitor hemoglobin levels 1, 3
Treatment Efficacy
Modern DAA regimens achieve sustained virological response (SVR) rates of 95-100% across all genotypes 1, 4, 5. In clinical trials:
- Sofosbuvir/velpatasvir achieved SVR rates of 98-100% in genotypes 1-6 5, 6
- Patients with advanced fibrosis or cirrhosis achieved SVR rates of 96-99% with sofosbuvir/velpatasvir 6
Safety Profile
- Most DAA regimens are well-tolerated with minimal side effects 1, 5
- Common adverse events include fatigue, headache, nausea, and nasopharyngitis 4, 7
- Sofosbuvir/velpatasvir plus voxilaprevir may cause more gastrointestinal symptoms than sofosbuvir/velpatasvir alone 7
Important Cautions
- Protease inhibitors (glecaprevir, voxilaprevir) are contraindicated in decompensated cirrhosis 2
- Drug interactions: Avoid co-administration of DAAs with potent inducers like St. John's Wort or rifampin 1
- HBV reactivation risk: Monitor HCV/HBV co-infected patients for hepatitis flare during and after treatment 3
Quality of Life Outcomes
Treatment with DAAs significantly improves patient-reported outcomes during treatment and after achieving SVR, with improvements in fatigue, work productivity, and overall quality of life 7.