What is the recommended treatment for patients with hepatitis C and chronic liver disease?

Recommended Treatment for Hepatitis C and Chronic Liver Disease

Direct-acting antiviral (DAA) therapy is the standard of care for all patients with chronic hepatitis C infection, with treatment regimens selected based on viral genotype, presence of cirrhosis, and prior treatment history. 1

Initial Patient Assessment

• Determine HCV genotype (1-6)
• Assess liver disease severity (no cirrhosis, compensated cirrhosis, or decompensated cirrhosis)
• Review treatment history (treatment-naïve or treatment-experienced)
• Test for HBV co-infection (HBsAg and anti-HBc) before starting treatment 1, 2

Treatment Recommendations by Genotype and Liver Status

Genotype 1,4,5, or 6

Without Cirrhosis or With Compensated Cirrhosis (Child-Pugh A):

• First-line options:
  • Sofosbuvir/velpatasvir for 12 weeks 1
  • Glecaprevir/pibrentasvir for 8 weeks (without cirrhosis) or 12 weeks (with cirrhosis) 3, 1
  • Ledipasvir/sofosbuvir for 12 weeks (can shorten to 8 weeks in treatment-naïve genotype 1 patients without cirrhosis if HCV RNA <6 million IU/mL) 1, 2, 4

With Decompensated Cirrhosis (Child-Pugh B or C):

• Ledipasvir/sofosbuvir + ribavirin for 12 weeks 1, 2, 5
• Sofosbuvir/velpatasvir + ribavirin for 12 weeks 1

Note: Protease inhibitors (glecaprevir, voxilaprevir) are contraindicated in decompensated cirrhosis 1

Genotype 3

Without Cirrhosis:

• Daclatasvir and sofosbuvir for 12 weeks 3
• Glecaprevir/pibrentasvir for 8 weeks 3
• Sofosbuvir/velpatasvir for 12 weeks 3, 6

With Cirrhosis:

• Daclatasvir, sofosbuvir, and ribavirin for 24 weeks 3
• Glecaprevir/pibrentasvir for 12 weeks 3
• Sofosbuvir/velpatasvir and ribavirin for 12 weeks 3, 6
• Sofosbuvir/velpatasvir/voxilaprevir for 8 weeks 3

Treatment for Special Populations

Liver Transplant Recipients:

• Ledipasvir/sofosbuvir + ribavirin for 12 weeks (genotype 1 or 4) 2

Treatment-Experienced Patients:

• For patients who have failed prior DAA therapy: sofosbuvir/velpatasvir/voxilaprevir for 12 weeks 1
• For patients who have failed interferon-based therapy: follow genotype-specific recommendations above with potentially longer treatment durations 3, 1

Monitoring During Treatment

• Monitor for HBV reactivation in HBV/HCV co-infected patients 1, 2
• Monitor hemoglobin levels for patients on ribavirin-containing regimens 1
• Avoid coadministration of DAAs with potent inducers like St. John's Wort or rifampin 1

Treatment Efficacy

Modern DAA regimens achieve sustained virological response (SVR) rates of 95-100% across all genotypes 1:

• Sofosbuvir/velpatasvir: 97-99% SVR in genotypes 1-6 with advanced fibrosis/cirrhosis 6
• Ledipasvir/sofosbuvir: 96-98% SVR in genotype 1 patients 4, 7
• Glecaprevir/pibrentasvir: 95-100% SVR across genotypes 3

Common Pitfalls and Caveats

• HBV reactivation risk: Test all patients for HBV before starting treatment and monitor HBV/HCV co-infected patients during and after treatment 1, 2
• Drug interactions: Carefully review all medications, especially acid-reducing agents (proton pump inhibitors) which can reduce efficacy of some DAAs 4
• Treatment duration: Don't unnecessarily extend treatment beyond recommended durations - studies show 8-week regimens are effective for eligible patients 4
• Ribavirin dosing: For patients requiring ribavirin, weight-based dosing is recommended (1000 mg for <75 kg, 1200 mg for ≥75 kg) with dose reductions for those with renal impairment or anemia 2
• Protease inhibitor contraindication: Avoid protease inhibitors (glecaprevir, voxilaprevir) in patients with decompensated cirrhosis 1

The landscape of hepatitis C treatment has dramatically evolved from interferon-based therapies with low efficacy and significant side effects to highly effective DAA regimens with minimal adverse effects and shorter treatment durations, making HCV the first chronic viral infection potentially eradicable worldwide 8.