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
Treatment Options
- Sofosbuvir/velpatasvir (400 mg/100 mg) is administered as a single tablet once daily for 12 weeks, with or without food 2
- Glecaprevir/pibrentasvir is administered as 3 tablets once daily with food for 8-12 weeks 1
- For patients with genotype 1a, sofosbuvir/velpatasvir for 12 weeks achieves a 98% sustained virological response (SVR) rate 1
- For patients with genotype 1b, either sofosbuvir/velpatasvir for 12 weeks or grazoprevir/elbasvir for 12 weeks are effective options 1
Treatment Duration Based on Patient Factors
- For treatment-naïve patients without cirrhosis: glecaprevir/pibrentasvir for 8 weeks or sofosbuvir/velpatasvir for 12 weeks 3
- For treatment-naïve patients with compensated cirrhosis: glecaprevir/pibrentasvir for 8 weeks or sofosbuvir/velpatasvir for 12 weeks 3
- For treatment-experienced patients without cirrhosis: sofosbuvir/velpatasvir for 12 weeks or glecaprevir/pibrentasvir for 8-12 weeks (depending on genotype) 3
- For treatment-experienced patients with compensated cirrhosis: sofosbuvir/velpatasvir for 12 weeks or glecaprevir/pibrentasvir for 12 weeks 3
Special Populations
- For patients with decompensated cirrhosis (Child-Pugh B or C): sofosbuvir/velpatasvir plus ribavirin for 12 weeks 2, 1
- For patients with severe renal impairment (eGFR <30 ml/min/1.73 m²): glecaprevir/pibrentasvir is preferred as sofosbuvir-based regimens should be used with caution 3
- For HIV/HCV co-infected patients: same regimens as HCV mono-infected patients, with attention to potential drug interactions with antiretroviral therapy 3
Pre-Treatment Assessment
- HCV RNA quantitative testing and genotyping/subtyping should be performed prior to initiating treatment 1
- Assessment of liver disease severity is essential to guide therapy decisions and predict prognosis 1
- All patients should be tested for evidence of current or prior HBV infection by measuring HBsAg and anti-HBc before starting HCV treatment 2
- Screen for potential drug-drug interactions with all concurrent medications 1
Treatment Monitoring
- SVR12 (undetectable HCV RNA 12 weeks after treatment completion) represents cure of infection in more than 99% of patients 1
- Monitor for HBV reactivation in HCV/HBV co-infected patients during and after DAA therapy 2
- On-treatment viral load monitoring is no longer required due to high efficacy and low viral breakthrough rates of current DAA regimens 3
Benefits of Treatment
- Achieving SVR reduces the risk of liver-related complications including cirrhosis progression, hepatocellular carcinoma, and mortality 3
- SVR is associated with improvement in liver histology, decreased risk of cirrhotic complications, and resolution of extrahepatic manifestations 1
- Treatment should be prioritized for patients with advanced fibrosis (≥F3) including compensated and decompensated cirrhosis 4
- Treatment should also be prioritized in the pre- and post-liver transplant setting and for patients with severe extrahepatic manifestations 4
Common Pitfalls and Caveats
- The presence of baseline resistance-associated substitutions (RASs) may affect treatment response and require adjustment of treatment duration or addition of ribavirin 1
- Patients with cirrhosis who achieve SVR still require monitoring for hepatocellular carcinoma with ultrasound every 6 months 5
- Protease inhibitor-containing regimens (glecaprevir/pibrentasvir) should not be used in patients with decompensated cirrhosis 3
- Test all patients for HBV before starting treatment, as HBV reactivation has been reported in HCV/HBV co-infected patients undergoing DAA therapy 2