First-Line Medications for Treating Active Hepatitis C
The recommended first-line medications for treating active hepatitis C are pangenotypic direct-acting antiviral (DAA) regimens, specifically sofosbuvir/velpatasvir for 12 weeks or glecaprevir/pibrentasvir for 8-12 weeks depending on cirrhosis status and treatment history. 1, 2
Pangenotypic Treatment Options
- Sofosbuvir/velpatasvir (400 mg/100 mg) once daily for 12 weeks is recommended as a first-line pangenotypic regimen for treatment-naïve and treatment-experienced patients with all HCV genotypes (1-6), with or without compensated cirrhosis 3
- Glecaprevir/pibrentasvir is indicated for treatment of adult and pediatric patients 3 years and older with chronic HCV genotype 1-6 infection without cirrhosis (8 weeks) or with compensated cirrhosis (12 weeks) 4, 5
- Both regimens have demonstrated high sustained virologic response (SVR) rates exceeding 95% across different genotypes 1, 2
Genotype-Specific Treatment Options
Genotype 1
- Ledipasvir/sofosbuvir (90 mg/400 mg) once daily for 12 weeks (can be shortened to 8 weeks in treatment-naïve patients without cirrhosis and HCV RNA <6 million IU/mL) 3, 6
- Elbasvir/grazoprevir once daily for 12 weeks (for patients without NS5A resistance-associated substitutions) 3, 5
- Sofosbuvir and daclatasvir combination for 12 weeks without ribavirin in treatment-naïve patients 3
Genotype 2
- Sofosbuvir/velpatasvir for 12 weeks without ribavirin 3, 2
- Sofosbuvir and daclatasvir combination for 12 weeks 3
Genotype 3
- Sofosbuvir/velpatasvir for 12 weeks (may need ribavirin addition in cirrhotic or treatment-experienced patients) 3, 2
- Daclatasvir and sofosbuvir for 12 weeks in non-cirrhotic patients; 24 weeks with ribavirin in cirrhotic patients 3
Genotype 4,5, and 6
- Sofosbuvir/velpatasvir for 12 weeks without ribavirin 3, 2
- Ledipasvir/sofosbuvir for 12 weeks 3, 7
- Elbasvir/grazoprevir for 12 weeks (genotype 4) 3
- Ombitasvir/paritaprevir/ritonavir with ribavirin for 12 weeks (genotype 4) 3
Treatment Duration Considerations
- For patients without cirrhosis: generally shorter treatment durations (8 weeks with glecaprevir/pibrentasvir) 5, 4
- For patients with compensated cirrhosis: usually 12-week regimens 5, 3
- For treatment-experienced patients: may require longer treatment duration or addition of ribavirin 3
Special Populations
- HIV co-infected patients: Same HCV treatment regimens as in patients without HIV infection, with dose adjustments for potential drug interactions with antiretroviral medications 1, 2
- Decompensated cirrhosis: Sofosbuvir-based regimens (avoid protease inhibitors like glecaprevir/pibrentasvir) 3, 2
- Liver transplant recipients: Sofosbuvir/velpatasvir for 12 weeks or other sofosbuvir-based regimens 3, 2
Monitoring and Precautions
- Test all patients for evidence of current or prior HBV infection before initiating treatment to prevent HBV reactivation 4
- Monitor HCV RNA levels at baseline, during treatment, at the end of treatment, and 12 weeks after completion to assess SVR 5
- For patients with cirrhosis, continue monitoring for hepatocellular carcinoma with ultrasound every 6 months, even after achieving SVR 1, 2
- Carefully evaluate drug-drug interactions before initiating DAA therapy, particularly in patients on multiple medications 2
Common Pitfalls
- Failing to screen for HBV co-infection before starting treatment 4
- Inappropriate shortening of treatment duration in patients with cirrhosis or prior treatment failure 3
- Not considering drug interactions, especially with acid-reducing medications which can reduce efficacy of some regimens 6
- Overlooking the need for ribavirin in certain patient populations (treatment-experienced, cirrhotic) 3