What is the recommended treatment regimen for hepatitis C (HCV)?

Treatment of Hepatitis C Virus Infection

The recommended first-line treatment for hepatitis C is sofosbuvir/velpatasvir (400mg/100mg) once daily for 12 weeks, which is effective across all HCV genotypes (1-6) regardless of cirrhosis status or treatment experience. 1

Treatment Approach Based on HCV Genotype

Genotype 1-6 (Treatment-Naïve and Treatment-Experienced)

• First-line regimen: Sofosbuvir/velpatasvir for 12 weeks without ribavirin for patients without cirrhosis or with compensated cirrhosis (Child-Pugh A) 2, 1, 3
• Alternative regimen: Glecaprevir/pibrentasvir for 8 weeks for patients without cirrhosis 1, 4

Special Considerations for Genotype 3

• For treatment-naïve patients without cirrhosis: Sofosbuvir/velpatasvir for 12 weeks without ribavirin 2
• For treatment-experienced patients without cirrhosis or patients with compensated cirrhosis: If NS5A resistance testing is available:
  • With Y93H mutation: Sofosbuvir/velpatasvir plus ribavirin for 12 weeks 2, 1
  • Without Y93H mutation: Sofosbuvir/velpatasvir for 12 weeks without ribavirin 2, 1
• If NS5A resistance testing is not available: Sofosbuvir/velpatasvir plus ribavirin for 12 weeks 2

Patients with Decompensated Cirrhosis (Child-Pugh B or C)

• Sofosbuvir/velpatasvir plus ribavirin for 12 weeks 3
• Ribavirin dosing: 1,000 mg/day for patients <75 kg and 1,200 mg/day for patients ≥75 kg, divided into two doses 3

Efficacy of Recommended Regimens

Sofosbuvir/velpatasvir has demonstrated excellent efficacy across all genotypes:

• In the ASTRAL-1 trial, SVR12 rates were 98% (323/328) in genotype 1, including 98% (206/210) in genotype 1a and 99% (117/118) in genotype 1b 2
• For genotype 2, SVR12 rates were high with sofosbuvir/velpatasvir for 12 weeks 5
• For genotype 3, the ASTRAL-3 trial showed SVR12 rates of 98% (160/163) in treatment-naïve patients without cirrhosis, 93% (40/43) in treatment-naïve patients with cirrhosis, 91% (31/34) in treatment-experienced patients without cirrhosis, and 89% (33/37) in treatment-experienced patients with cirrhosis 2
• For genotypes 4,5, and 6, sofosbuvir/velpatasvir achieved SVR12 rates of 100% (116/116), 97% (34/35), and 100% (41/41), respectively 2, 5

Monitoring During Treatment

• Test all patients for evidence of current or prior HBV infection (HBsAg and anti-HBc) before initiating HCV treatment to prevent HBV reactivation 4, 3
• No specific stopping rules (futility rules) have been defined for sofosbuvir/velpatasvir regimens 2
• Use a sensitive PCR-based assay with a lower limit of detection of <15 IU/ml to monitor HCV RNA levels 2
• Monitor HCV RNA at baseline, week 4, end of treatment (week 12), and 12 weeks after completion of therapy to assess SVR12 2

Important Clinical Considerations

• Sofosbuvir/velpatasvir can be taken with or without food 3
• No dose adjustments are needed for patients with renal impairment 3
• Drug-drug interactions should be carefully assessed, particularly with acid-reducing agents, amiodarone, and certain anticonvulsants 6
• For patients with contraindications to ribavirin or poor tolerance, consider extending treatment duration to 24 weeks 2, 1

Advantages of Sofosbuvir/Velpatasvir

• Pangenotypic activity eliminates the need for genotype testing before treatment initiation 7
• Once-daily, single-tablet regimen improves adherence 6
• High efficacy across diverse patient populations, including those with compensated cirrhosis or HIV co-infection 8, 9
• Well-tolerated with low rates of serious adverse events (2%) 5

The evolution of HCV treatment has led to these highly effective, well-tolerated, all-oral regimens that have revolutionized the management of hepatitis C, with sofosbuvir/velpatasvir representing the current standard of care due to its pangenotypic activity and high cure rates.