Recommended Treatment for Hepatitis C (HCV)
The recommended first-line treatment for chronic hepatitis C virus (HCV) infection 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 Recommendations Based on Patient Characteristics
For Patients Without Cirrhosis:
Treatment-naïve and treatment-experienced patients with HCV genotypes 1a, 1b, 2,4,5, or 6 should receive either:
- Sofosbuvir/velpatasvir for 12 weeks, OR
- Glecaprevir/pibrentasvir for 8 weeks 1
Treatment-naïve patients with genotype 3 without cirrhosis should receive either:
- Sofosbuvir/velpatasvir for 12 weeks, OR
- Glecaprevir/pibrentasvir for 8 weeks 1
Treatment-experienced patients with genotype 3 without cirrhosis should receive either:
- Sofosbuvir/velpatasvir for 12 weeks, OR
- Glecaprevir/pibrentasvir for 12 weeks 1
For Patients With Compensated Cirrhosis (Child-Pugh A):
Treatment-naïve patients with genotypes 1a, 1b, 2,4,5, or 6 should receive either:
- Sofosbuvir/velpatasvir for 12 weeks, OR
- Glecaprevir/pibrentasvir for 8 weeks 1
Treatment-experienced patients with genotypes 1a, 1b, 2,4,5, or 6 with compensated cirrhosis should receive either:
- Sofosbuvir/velpatasvir for 12 weeks, OR
- Glecaprevir/pibrentasvir for 12 weeks 1
Treatment-naïve patients with genotype 3 with compensated cirrhosis should receive one of:
- Sofosbuvir/velpatasvir with weight-based ribavirin for 12 weeks, OR
- Sofosbuvir/velpatasvir/voxilaprevir for 12 weeks, OR
- Glecaprevir/pibrentasvir for 12 weeks (can be shortened to 8 weeks in some cases) 1
Treatment-experienced patients with genotype 3 with compensated cirrhosis should receive one of:
- Sofosbuvir/velpatasvir with weight-based ribavirin for 12 weeks, OR
- Sofosbuvir/velpatasvir/voxilaprevir for 12 weeks, OR
- Glecaprevir/pibrentasvir for 16 weeks 1
Special Considerations
HBV Co-infection
- Test all patients for evidence of current or prior HBV infection before initiating HCV treatment by measuring HBsAg and anti-HBc 2, 3
- HBV reactivation has been reported in HCV/HBV co-infected patients who were undergoing or had completed treatment with HCV direct-acting antivirals 2, 3
- Monitor HCV/HBV co-infected patients for hepatitis flare or HBV reactivation during and after HCV treatment 2, 3
HIV Co-infection
- The same HCV treatment regimens can be used in HIV-coinfected patients as in patients without HIV infection, as the virological results of therapy are identical 1
- Dose adjustments may be needed in case of interactions with antiretroviral drugs 1
Genotype Testing
- In settings where HCV genotype and subtype determination are available and affordable, this information remains useful to optimize the virological results of HCV therapy 1
- For patients with infrequent subtypes (1l, 4r, 3b, 3g, 6u, 6v) or those harboring multiple NS5A resistance-associated substitutions (RASs), consider first-line treatment with sofosbuvir/velpatasvir/voxilaprevir 1
Important Monitoring and Precautions
- For patients with cirrhosis, even after achieving sustained virologic response (SVR), continue monitoring for hepatocellular carcinoma with ultrasound every 6 months 4
- Despite achieving SVR, the risk of hepatocellular carcinoma or complications of chronic liver disease still exists in patients with cirrhosis or advanced hepatic fibrosis 4
- Cirrhotic patients often have hematological problems due to portal hypertension and splenomegaly, requiring careful monitoring during treatment 4
Evolution of HCV Treatment
HCV treatment has evolved dramatically from interferon-based regimens with low efficacy and significant side effects to highly effective, well-tolerated oral DAA combinations:
- Older regimens using pegylated interferon and ribavirin achieved SVR rates of only 10-20% with significant side effects 5
- Modern DAA regimens achieve SVR rates >95% for most genotypes with minimal side effects and shorter treatment durations 6
- The fixed-dose combination of ledipasvir/sofosbuvir was one of the first highly effective oral regimens but has been largely replaced by pangenotypic options 7, 8
The current pangenotypic regimens (sofosbuvir/velpatasvir and glecaprevir/pibrentasvir) represent a significant advancement in HCV treatment, offering high cure rates across all genotypes with excellent safety profiles and shorter treatment durations.