What is the recommended treatment regimen for Hepatitis C?

Recommended Treatment Regimen for Hepatitis C

The recommended first-line treatment for hepatitis C is a pangenotypic direct-acting antiviral (DAA) regimen consisting of either sofosbuvir/velpatasvir for 12 weeks or glecaprevir/pibrentasvir for 8-12 weeks, depending on cirrhosis status and treatment history. 1, 2

Treatment Based on HCV Genotype

Genotype 1

• For genotype 1a patients without cirrhosis, options include:

  • Daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) for 12 weeks 3
  • Daily sofosbuvir (400 mg) plus simeprevir (150 mg) for 12 weeks (if Q80K variant negative) 3
  • Sofosbuvir/velpatasvir for 12 weeks (98% SVR rate) 2, 4

• For genotype 1b patients without cirrhosis:

  • Daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) for 12 weeks 3
  • Daily fixed-dose combination of paritaprevir/ritonavir/ombitasvir plus dasabuvir for 12 weeks 3
  • Sofosbuvir/velpatasvir for 12 weeks 3

Genotype 2

• Sofosbuvir/velpatasvir for 12 weeks without ribavirin 3
• Sofosbuvir and daclatasvir for 12 weeks without ribavirin 3

Genotype 3

• Sofosbuvir/velpatasvir for 12 weeks (treatment-naïve without cirrhosis) 3
• Sofosbuvir/velpatasvir plus ribavirin for 12 weeks (treatment-experienced or with cirrhosis) 3
• Sofosbuvir/velpatasvir/voxilaprevir for 8 weeks (especially for patients with cirrhosis) 3

Genotype 4,5, and 6

• Sofosbuvir/velpatasvir for 12 weeks without ribavirin 3, 4
• Fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) for 12 weeks 3

Treatment Duration Considerations

• Without cirrhosis:

  • Glecaprevir/pibrentasvir for 8 weeks 3, 2
  • Sofosbuvir/velpatasvir for 12 weeks 4

• With compensated cirrhosis:

  • Glecaprevir/pibrentasvir for 12 weeks 3, 2
  • Sofosbuvir/velpatasvir for 12 weeks 4

• With decompensated cirrhosis:

  • Sofosbuvir/velpatasvir plus ribavirin for 12 weeks 2, 4

Special Populations

HIV Co-infection

• The same HCV treatment regimens can be used in HIV-coinfected patients as in patients without HIV infection, with dose adjustments needed in case of interactions with antiretroviral drugs 1, 2
• Daclatasvir dosage must be adjusted to 30 mg in patients receiving ritonavir- or cobicistat-boosted atazanavir or cobicistat-boosted elvitegravir, and to 90 mg in patients receiving efavirenz 2

Liver Transplant Recipients

• For treatment-naïve and treatment-experienced liver transplant recipients without cirrhosis or with compensated cirrhosis (Child-Pugh A), sofosbuvir/velpatasvir once daily for 12 weeks is recommended 4

Monitoring and Precautions

• Test all patients for evidence of current or prior HBV infection before initiating HCV treatment by measuring HBsAg and anti-HBc 4
• Monitor HCV RNA levels at baseline, during treatment, at the end of treatment, and 12 weeks after completion to assess SVR 2
• For patients with cirrhosis, continue monitoring for hepatocellular carcinoma with ultrasound every 6 months, even after achieving SVR 1, 2

Common Pitfalls and Caveats

• Drug-drug interactions must be carefully evaluated before initiating DAA therapy, particularly in patients on multiple medications 2
• Patients with HCV genotype 1a who have the NS3 Q80K polymorphism have lower SVR rates with sofosbuvir and simeprevir; in these patients, one of the other recommended regimens should be used 3
• HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct-acting antivirals; monitor for hepatitis flare or HBV reactivation during and after treatment 4

The evolution of hepatitis C treatment has moved from interferon-based regimens to highly effective, well-tolerated, all-oral DAA combinations that achieve SVR rates exceeding 95% in most patient populations 2, 5, 6. Modern pangenotypic regimens have simplified treatment by eliminating the need for genotype testing in many settings, though genotype information remains useful to optimize therapy in some cases 1.