What is the treatment for hepatitis C?

Treatment for Hepatitis C

The standard of care for hepatitis C treatment is direct-acting antiviral (DAA) therapy, with specific regimens selected based on viral genotype, with sofosbuvir/velpatasvir for 12 weeks being the recommended pangenotypic regimen for all HCV genotypes (1-6). 1

First-Line Treatment Options

Pangenotypic Regimens (for all genotypes)

• Sofosbuvir/velpatasvir for 12 weeks 2, 1
  • Highly effective across all genotypes with SVR rates >95%
  • Suitable for both treatment-naïve and treatment-experienced patients
  • Can be used in patients with or without compensated cirrhosis

Genotype-Specific Options

1. For Genotype 1:

   • Sofosbuvir/ledipasvir for 12 weeks (8 weeks may be sufficient for treatment-naïve non-cirrhotic patients with viral load <6 million IU/mL) 2
   • Glecaprevir/pibrentasvir for 8-12 weeks 1, 3
   • Elbasvir/grazoprevir for 12 weeks 1

2. For Genotype 2:

   • Sofosbuvir/velpatasvir for 12 weeks 2
   • Glecaprevir/pibrentasvir for 8 weeks 3

3. For Genotype 3:

   • Sofosbuvir/velpatasvir for 12 weeks (add ribavirin if NS5A Y93H mutation present) 2
   • Glecaprevir/pibrentasvir for 8-16 weeks (duration depends on treatment experience and cirrhosis status) 3

4. For Genotypes 4,5, and 6:

   • Sofosbuvir/velpatasvir for 12 weeks 2
   • Glecaprevir/pibrentasvir for 8-12 weeks 3

Treatment Considerations

Pre-Treatment Assessment

• HCV genotype and subtype determination 2
• Assessment of liver disease severity (fibrosis stage) 2
• Evaluation for potential drug-drug interactions 1
• Testing for HCV RNA viral load 2

Treatment Duration

• 8-12 weeks for most patients without cirrhosis 1
• 12-24 weeks for patients with compensated cirrhosis or prior treatment failure 2
• Ribavirin may be added for difficult-to-treat patients (e.g., those with cirrhosis or prior treatment failure) 2

Monitoring During Treatment

• Assess adherence at each visit
• Monitor for adverse effects
• Check HCV RNA 12 weeks after completing therapy to confirm SVR (cure) 2, 1

Special Populations

Patients with Cirrhosis

• May require longer treatment duration (12-24 weeks) 2
• May benefit from addition of ribavirin 2
• Continued HCC surveillance every 6 months even after achieving SVR 1

HIV/HCV Coinfection

• Same regimens as HCV monoinfection with attention to potential drug interactions with antiretroviral therapy 2
• High SVR rates (>95%) reported in clinical trials 3

Post-Transplant Patients

• DAA therapy is highly effective (SVR rates >95%) 3
• Careful monitoring of immunosuppressant levels required due to potential drug interactions 3

Renal Impairment

• Glecaprevir/pibrentasvir is preferred for severe renal impairment (GFR <30 mL/min) 3
• Some DAAs require dose adjustment or are contraindicated in severe renal impairment 2

Treatment Failures

For patients who fail initial DAA therapy:

• Resistance testing may guide retreatment options 2
• Retreatment with a different DAA combination for 12-24 weeks with addition of ribavirin 2
• Consider referral to a specialist with experience in managing treatment failures 1

Historical Context

The treatment landscape for hepatitis C has evolved dramatically:

• Pre-2014: Pegylated interferon plus ribavirin (low efficacy, significant side effects) 2, 4
• 2014-2015: First-generation DAAs combined with pegylated interferon and ribavirin 2
• 2016-present: All-oral DAA combinations with >95% cure rates and minimal side effects 5, 6

The goal of therapy is to achieve sustained virological response (SVR), which is associated with resolution of liver disease in non-cirrhotic patients and reduced risk of complications in cirrhotic patients 1.