Treatment Plan for Hepatitis C
For most hepatitis C patients without cirrhosis or with compensated cirrhosis, treat with sofosbuvir/velpatasvir 400mg/100mg once daily for 12 weeks, or glecaprevir/pibrentasvir 100mg/40mg (3 tablets) once daily for 8 weeks (treatment-naïve without cirrhosis) or 12 weeks (treatment-experienced or with compensated cirrhosis). 1
Pre-Treatment Assessment
You need only three pieces of information before starting treatment:
- Confirm active HCV infection: HCV RNA or HCV core antigen test (positive result required)
- Assess for cirrhosis: Use FIB-4 or APRI score (non-invasive markers) to determine if cirrhosis is present
- Check drug-drug interactions: Review all current medications for potential interactions 1
Genotype testing is NOT required for the simplified treatment approach, which is now the preferred strategy to improve access to care 1.
Treatment Regimens by Patient Category
Treatment-Naïve Patients WITHOUT Cirrhosis
Option 1 (Preferred): Glecaprevir/pibrentasvir for 8 weeks 1
- Dosing: 3 tablets (100mg/40mg each) once daily with food
Option 2: Sofosbuvir/velpatasvir for 12 weeks 1
- Dosing: 1 tablet (400mg/100mg) once daily with or without food
Treatment-Naïve Patients WITH Compensated Cirrhosis (Child-Pugh A)
Option 1: Sofosbuvir/velpatasvir for 12 weeks 1
- Dosing: 1 tablet (400mg/100mg) once daily
Option 2: Glecaprevir/pibrentasvir for 12 weeks 1
- Dosing: 3 tablets (100mg/40mg each) once daily with food
Treatment-Experienced Patients WITHOUT Cirrhosis
Same as treatment-naïve without cirrhosis:
- Glecaprevir/pibrentasvir for 8 weeks, OR
- Sofosbuvir/velpatasvir for 12 weeks 1
Treatment-Experienced Patients WITH Compensated Cirrhosis
Both regimens require 12 weeks:
- Sofosbuvir/velpatasvir for 12 weeks, OR
- Glecaprevir/pibrentasvir for 12 weeks 1
Important Caveats and Pitfalls
Genotype 3 with cirrhosis: These patients may have slightly lower cure rates, but effective retreatment options exist if initial therapy fails 1.
If cirrhosis status is unknown: Use a universal duration of 12 weeks regardless of which regimen you choose 1.
Drug-drug interactions: This is critical—carefully review all medications, particularly:
- Acid-reducing agents (can affect absorption)
- Anticonvulsants
- HIV medications
- Cardiac medications
- Herbal supplements
Decompensated cirrhosis (Child-Pugh B or C): These recommendations do NOT apply—these patients require specialist consultation and different regimens.
Post-Treatment Monitoring
SVR12 testing can be omitted in most adherent patients given the high cure rates (>95%) with these regimens 1.
Exception: Test for SVR12 (HCV RNA at 12 weeks post-treatment) in patients with:
- High-risk behaviors for reinfection (active injection drug use, men who have sex with men)
- These patients need yearly testing thereafter 1
Patients with cirrhosis: Even after cure, continue HCC surveillance every 6 months indefinitely (ultrasound ± AFP).
Alternative Genotype-Specific Approach (If Genotype Known)
If genotype testing is available and affordable, the 2015 AASLD-IDSA guidelines provide genotype-specific alternatives 2:
Genotype 1: Ledipasvir/sofosbuvir 90mg/400mg once daily for 12 weeks Genotype 2: Sofosbuvir 400mg + weight-based ribavirin for 12 weeks (16 weeks if cirrhosis) Genotype 3: More challenging—sofosbuvir + ribavirin for 24 weeks Genotype 4,5,6: Ledipasvir/sofosbuvir for 12 weeks
However, the pangenotypic simplified approach from 2020 is now preferred as it eliminates the need for genotyping and achieves excellent results across all genotypes 1.