Treatment for Hepatitis C
The first-line treatment for 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, 2, 3
Recommended Treatment Regimens
First-line options:
- Sofosbuvir/velpatasvir (fixed-dose combination of 400 mg sofosbuvir and 100 mg velpatasvir) in a single tablet administered once daily for 12 weeks 1
- Glecaprevir/pibrentasvir (fixed-dose combination of 300 mg glecaprevir and 120 mg pibrentasvir) in 3 tablets administered once daily with food for 8-12 weeks 1
Alternative options:
- For genotype 1b specifically: grazoprevir/elbasvir (fixed-dose combination of 100 mg grazoprevir and 50 mg elbasvir) in a single tablet administered once daily 1
- In low and middle-income countries where the above options are unavailable or unaffordable: generic sofosbuvir and daclatasvir according to 2016 EASL recommendations 1
Treatment Selection Based on Patient Factors
Genotype-specific considerations:
- Genotype 1a: Sofosbuvir/velpatasvir for 12 weeks (SVR rate 98%) 1, 3
- Genotype 1b: Sofosbuvir/velpatasvir for 12 weeks or grazoprevir/elbasvir for 12 weeks 1
- Genotype 2: Sofosbuvir/velpatasvir for 12 weeks 1, 3
- Genotype 3: Sofosbuvir/velpatasvir for 12 weeks 1, 3
- Genotype 4-6: Sofosbuvir/velpatasvir for 12 weeks 1
Cirrhosis status:
- No cirrhosis: Standard duration as above 1
- Compensated cirrhosis (Child-Pugh A): May require extended duration to 12 weeks for glecaprevir/pibrentasvir 1, 3
- Decompensated cirrhosis: Sofosbuvir/velpatasvir plus ribavirin for 12 weeks 3
Special populations:
- HIV co-infection: Same regimens as HCV monoinfection, but with careful attention to drug-drug interactions with antiretroviral therapy 1, 3
- Severe renal impairment: No specific dosage recommendations can be made for sofosbuvir in severe renal impairment or end-stage renal disease 4
- Prior treatment failure: Sofosbuvir/velpatasvir/voxilaprevir for 12 weeks 1, 5
Pre-Treatment Assessment
- HCV RNA quantitative testing and genotyping/subtyping should be performed prior to initiating treatment 1, 2
- Assessment of liver disease severity is essential to guide therapy decisions and predict prognosis 1, 2
- Test all patients for HBV infection by measuring HBsAg and anti-HBc before starting treatment 4
- Screen for potential drug-drug interactions with all concurrent medications 2, 4
Treatment Monitoring
- Monitor HCV RNA levels at baseline, during treatment, at the end of treatment, and 12 weeks after completion to assess SVR 2, 3
- SVR12 (undetectable HCV RNA 12 weeks after treatment completion) represents cure of infection in more than 99% of patients 2
- For patients with cirrhosis, continued monitoring for hepatocellular carcinoma with ultrasound every 6 months is recommended, even after achieving SVR 2
Treatment Efficacy and Outcomes
- Modern DAA regimens achieve SVR rates exceeding 95% in most patient populations 1, 2, 6
- Successful eradication of HCV (achieving SVR) is associated with:
Common Pitfalls and Caveats
- HBV reactivation: HBV reactivation has been reported in HCV/HBV co-infected patients during or after DAA therapy, sometimes resulting in fulminant hepatitis, hepatic failure, and death 4
- Drug interactions: Carefully evaluate potential drug-drug interactions, particularly with amiodarone which may cause serious symptomatic bradycardia when combined with sofosbuvir-containing regimens 4
- Resistance-associated substitutions (RASs): In some cases, the presence of baseline RASs may affect treatment response and require adjustment of treatment duration or addition of ribavirin 1
- Continued HCC risk: Patients with cirrhosis who achieve SVR still require monitoring as they remain at risk for complications, though at significantly reduced rates 2