What is the recommended first-line treatment for chronic viral hepatitis C?

First-Line Treatment for Chronic Viral Hepatitis C

Direct-acting antiviral (DAA) regimens are the recommended first-line treatment for chronic hepatitis C, with specific regimens determined by HCV genotype, presence of cirrhosis, and prior treatment history. 1

Genotype-Specific Treatment Recommendations

Genotype 1 Infection

For patients with HCV genotype 1 (most common genotype):

• Ledipasvir/sofosbuvir for 12 weeks (can be shortened to 8 weeks in treatment-naïve patients without cirrhosis and with baseline HCV RNA <6 million IU/mL) 1, 2
• Elbasvir/grazoprevir for 12 weeks (for patients without NS5A resistance-associated substitutions) 1
• Glecaprevir/pibrentasvir for 8 weeks in non-cirrhotic patients and 12 weeks in patients with compensated cirrhosis 1, 3, 4
• Sofosbuvir/velpatasvir for 12 weeks (pangenotypic option) 1, 5, 6

Genotype 2 Infection

• Glecaprevir/pibrentasvir for 8 weeks in non-cirrhotic patients and 12 weeks in patients with compensated cirrhosis 1
• Sofosbuvir/velpatasvir for 12 weeks 1, 6
• Sofosbuvir plus ribavirin for 12 weeks (alternative option) 1

Genotype 3 Infection

• Sofosbuvir/velpatasvir for 12 weeks (may need ribavirin in cirrhotic patients) 1
• Glecaprevir/pibrentasvir for 8 weeks in non-cirrhotic patients and 12 weeks in patients with compensated cirrhosis 1, 3
• Daclatasvir plus sofosbuvir for 12 weeks (24 weeks with ribavirin for cirrhotic patients) 1

Genotype 4,5, or 6 Infection

• Ledipasvir/sofosbuvir for 12 weeks 1, 2
• Sofosbuvir/velpatasvir for 12 weeks 1, 6
• Glecaprevir/pibrentasvir for 8 weeks in non-cirrhotic patients and 12 weeks in patients with compensated cirrhosis 1, 3
• Elbasvir/grazoprevir for 12 weeks (genotype 4) 1

Special Considerations

Cirrhosis Status

• Non-cirrhotic patients: Generally require shorter treatment durations (8 weeks with glecaprevir/pibrentasvir) 1, 3
• Compensated cirrhosis: Usually require 12-week regimens 1, 3
• Decompensated cirrhosis: Ledipasvir/sofosbuvir plus ribavirin for 12 weeks or sofosbuvir/velpatasvir plus ribavirin for 12 weeks 1, 2

Prior Treatment Experience

• Treatment-naïve: Standard durations as listed above 1
• Treatment-experienced: May require longer treatment durations or addition of ribavirin 1
• NS5A inhibitor failures: Sofosbuvir/velpatasvir/voxilaprevir for 12 weeks 7

Monitoring During Treatment

• HCV RNA levels should be measured at baseline, week 4, week 12, at the end of treatment, and 12-24 weeks after completion to assess sustained virological response (SVR) 1
• Monitor for potential drug-drug interactions, particularly with HIV medications in co-infected patients 2, 5
• Test all patients for hepatitis B co-infection before starting treatment to prevent HBV reactivation 2

Practical Recommendations

• Pangenotypic regimens (sofosbuvir/velpatasvir or glecaprevir/pibrentasvir) are preferred when genotype testing is unavailable or in simplified treatment protocols 6, 4
• Ribavirin-free regimens are preferred when possible to avoid hemolytic anemia and other ribavirin-associated side effects 3, 6
• Single-tablet regimens improve adherence and should be prioritized when available 6

Cautions

• Check for potential drug interactions before initiating DAA therapy 2, 5
• Patients with decompensated cirrhosis should not receive protease inhibitor-containing regimens (glecaprevir/pibrentasvir, elbasvir/grazoprevir) 4
• Monitor for HBV reactivation in HBV/HCV co-infected patients 2

The goal of treatment is to achieve sustained virological response (SVR), which is defined as undetectable HCV RNA 12 weeks after completion of therapy and is considered a virological cure 1, 8.