What is the recommended treatment regimen for hepatitis C?

Treatment of Hepatitis C

The recommended first-line treatment for hepatitis C is the fixed-dose combination of sofosbuvir and velpatasvir for 12 weeks, regardless of genotype, for patients without cirrhosis or with compensated cirrhosis (Child-Pugh A). 1, 2

Treatment Regimens Based on Patient Characteristics

For patients without cirrhosis:

• Treatment-naïve patients (all genotypes): Sofosbuvir/velpatasvir for 12 weeks 1
• Treatment-experienced patients (all genotypes): Sofosbuvir/velpatasvir for 12 weeks 1
• Alternative option: Glecaprevir/pibrentasvir for 8 weeks for genotypes 1,2,4,5, or 6 2

For patients with compensated cirrhosis (Child-Pugh A):

• Treatment-naïve patients (all genotypes): Sofosbuvir/velpatasvir for 12 weeks 1
• Treatment-experienced patients (all genotypes): Sofosbuvir/velpatasvir for 12 weeks 1
• For genotype 3 specifically:
  • If NS5A resistance testing is available: Sofosbuvir/velpatasvir plus ribavirin for 12 weeks for those with Y93H mutation; Sofosbuvir/velpatasvir for 12 weeks for those without Y93H mutation 1
  • If NS5A resistance testing is unavailable: Sofosbuvir/velpatasvir plus ribavirin for 12 weeks 1

For patients with decompensated cirrhosis (Child-Pugh B or C):

• Sofosbuvir/velpatasvir plus weight-based ribavirin for 12 weeks 1, 3
• Note: Protease inhibitors (glecaprevir, pibrentasvir, voxilaprevir) are contraindicated in decompensated cirrhosis due to risk of toxicity 1

Dosing

• Adults: One tablet (400 mg sofosbuvir/100 mg velpatasvir) once daily with or without food 3
• Ribavirin dosing (when indicated): Weight-based at 1,000 mg daily for patients <75 kg and 1,200 mg daily for patients ≥75 kg, divided and administered twice daily with food 3

Efficacy

Sofosbuvir/velpatasvir has demonstrated excellent efficacy across all genotypes:

• Genotype 1: 98% SVR12 rate 2
• Genotype 2: >95% SVR12 rate 2
• Genotype 3: 93-98% SVR12 rate (varies by treatment history and cirrhosis status) 2
• Genotypes 4-6: >90% SVR12 rate 2

Monitoring During Treatment

• Test all patients for evidence of current or prior HBV infection before initiating treatment 3
• Monitor HCV RNA at baseline, week 4, end of treatment (week 12), and 12 weeks after completion of therapy 2
• No specific stopping rules have been defined for sofosbuvir/velpatasvir regimens 2

Special Considerations

HBV Coinfection

• Test all patients for HBV (HBsAg and anti-HBc) before starting treatment 3
• Monitor for HBV reactivation during and after treatment 3
• Consider antiviral therapy for HBV if indicated 3

Treatment Failures

For patients who have failed previous DAA therapy:

• Sofosbuvir/velpatasvir/voxilaprevir for 12 weeks 1
• Alternatively, sofosbuvir/velpatasvir plus ribavirin for 24 weeks 4

Common Pitfalls and Caveats

1. Failure to test for HBV: HBV reactivation can occur during or after HCV treatment, potentially leading to fulminant hepatitis or death 3

2. Inappropriate use of protease inhibitors in decompensated cirrhosis: Protease inhibitors are contraindicated in Child-Pugh B/C cirrhosis due to increased drug exposure and risk of toxicity 1

3. Overlooking drug interactions: Sofosbuvir/velpatasvir has important interactions with acid-reducing agents, certain anticonvulsants, and some antiretrovirals 5

4. Inadequate resistance testing for genotype 3 patients with cirrhosis: The presence of NS5A Y93H mutation significantly impacts treatment decisions for genotype 3 patients with cirrhosis 1

The evolution of hepatitis C treatment has dramatically improved outcomes, with current regimens achieving cure rates >95% with short duration, well-tolerated therapy. The pangenotypic activity of sofosbuvir/velpatasvir has simplified treatment by eliminating the need for genotype testing in many clinical scenarios.