What is the recommended treatment for patients with positive Hepatitis C (HCV) serology?

Treatment of Hepatitis C with Positive Serology

For patients with positive Hepatitis C (HCV) serology, direct-acting antiviral (DAA) therapy is recommended based on the specific HCV genotype, with treatment durations of 8-24 weeks depending on patient characteristics and viral factors. 1

Initial Assessment Before Treatment

Before initiating HCV treatment:

• Test all patients for evidence of current or prior HBV infection by measuring hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) 2, 3
• Determine HCV genotype (1-6) as this guides treatment selection
• Assess for cirrhosis status (compensated vs. decompensated)
• Review treatment history (treatment-naïve vs. treatment-experienced)
• Check for potential drug interactions, especially in HIV co-infected patients

Treatment Recommendations by Genotype

Genotype 1 (Most Common)

First-line options:

1. Sofosbuvir/Ledipasvir:

   • Treatment-naïve without cirrhosis: 12 weeks (no ribavirin)
   • Can be shortened to 8 weeks if baseline HCV RNA <6 million IU/ml (use caution with F3 fibrosis) 1
   • Treatment-experienced with genotype 1b: 12 weeks (no ribavirin)
   • Treatment-experienced with genotype 1a: 12 weeks with ribavirin 1

2. Sofosbuvir/Velpatasvir:

   • 12 weeks for all patients (treatment-naïve and experienced, with or without cirrhosis) 1

3. Glecaprevir/Pibrentasvir (MAVYRET):

   • Treatment-naïve: 8 weeks regardless of cirrhosis status
   • Treatment-experienced with NS5A inhibitor: 16 weeks
   • Treatment-experienced with NS3/4A PI: 12 weeks 2

Genotype 2

1. Sofosbuvir/Velpatasvir:

   • 12 weeks for all patients (treatment-naïve and experienced, with or without cirrhosis) 1

2. Sofosbuvir/Daclatasvir:

   • 12 weeks for all patients (treatment-naïve and experienced, with or without cirrhosis) 1

3. Glecaprevir/Pibrentasvir:

   • Treatment-naïve: 8 weeks
   • Treatment-experienced: 8-12 weeks depending on cirrhosis status 2

Genotype 3

1. Sofosbuvir/Velpatasvir:

   • Treatment-naïve without cirrhosis: 12 weeks (no ribavirin)
   • Treatment-experienced or with cirrhosis: 12 weeks (consider adding ribavirin) 1

2. Sofosbuvir/Daclatasvir:

   • Treatment-naïve: 12 weeks
   • Treatment-experienced: 12 weeks with ribavirin or 24 weeks without ribavirin 1

Genotype 4,5, or 6

1. Sofosbuvir/Ledipasvir:

   • Treatment-naïve: 12 weeks (no ribavirin)
   • Treatment-experienced: 12 weeks with ribavirin or 24 weeks without ribavirin 1

2. Sofosbuvir/Velpatasvir:

   • 12 weeks for all patients (treatment-naïve and experienced, with or without cirrhosis) 1

3. Glecaprevir/Pibrentasvir:

   • Treatment-naïve: 8 weeks
   • Treatment-experienced: 8-12 weeks depending on cirrhosis status 2

Special Populations

HIV Co-infection

• Use the same regimens as in HCV mono-infected patients
• Check for drug interactions with antiretroviral medications 1

HBV Co-infection

• Monitor for HBV reactivation during and after HCV treatment
• Consider HBV treatment if reactivation occurs 3

Decompensated Cirrhosis

• Avoid protease inhibitor-containing regimens
• Prefer Sofosbuvir-based regimens with ribavirin

Important Considerations and Potential Pitfalls

1. HBV Reactivation: Patients with current or prior HBV infection may experience reactivation during or after HCV treatment, which can lead to severe hepatitis, liver failure, and death. Monitor HBV markers before and during treatment 3.

2. Drug Interactions:

   • Amiodarone with sofosbuvir-containing regimens can cause serious symptomatic bradycardia 3
   • P-gp inducers (rifampin, St. John's wort) can reduce DAA effectiveness 3
   • Proton pump inhibitors may reduce treatment efficacy 4

3. Treatment Duration: Avoid unnecessarily prolonged treatment. Many patients qualify for 8-week regimens but receive 12 weeks of therapy 5.

4. Ribavirin Considerations: When used, ribavirin dosing is weight-based (1000 mg daily if <75 kg, 1200 mg daily if ≥75 kg) and requires pregnancy avoidance 1, 3.

5. Post-treatment Monitoring: Check for SVR12 (sustained virologic response 12 weeks after completing therapy) to confirm cure.

Current DAA regimens achieve SVR rates >95% in most patient populations, representing a significant improvement over historical interferon-based therapies 4, 5.