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

Hepatitis C Treatment

The recommended first-line treatment for chronic Hepatitis C is a pangenotypic direct-acting antiviral (DAA) regimen: either sofosbuvir/velpatasvir (400mg/100mg) once daily for 12 weeks or glecaprevir/pibrentasvir for 8-12 weeks depending on cirrhosis status, both effective across all HCV genotypes 1-6. 1, 2, 3

Preferred Pangenotypic Regimens

Sofosbuvir/Velpatasvir (First-Line Option)

• Single-tablet, once-daily regimen effective for all genotypes (1-6) with sustained virologic response (SVR) rates of 95-100% 1, 2, 4
• Treatment-naïve and treatment-experienced patients without cirrhosis or with compensated cirrhosis (Child-Pugh A): 12 weeks without ribavirin 5, 1, 2
• Patients with decompensated cirrhosis (Child-Pugh B or C): 12 weeks with weight-based ribavirin (1000mg if <75kg, 1200mg if ≥75kg) 2, 6
• HIV-coinfected patients: Same regimen as HCV monoinfection (12 weeks) 1, 2
• Liver transplant recipients without cirrhosis or with compensated cirrhosis: 12 weeks 2

Glecaprevir/Pibrentasvir (Alternative First-Line)

• Treatment-naïve patients without cirrhosis: 8 weeks for all genotypes 1, 3
• Treatment-naïve patients with compensated cirrhosis: 8 weeks for all genotypes 1, 3
• Treatment-experienced patients without cirrhosis previously treated with peginterferon/ribavirin/sofosbuvir (no prior NS3/4A PI or NS5A inhibitor): 8 weeks for genotypes 1,2,4,5,6; 16 weeks for genotype 3 3
• Treatment-experienced patients with compensated cirrhosis: 12 weeks for genotypes 1,2,4,5,6; 16 weeks for genotype 3 3

Genotype-Specific Considerations

Genotype 1 (Alternative Regimens if Pangenotypic Options Unavailable)

• Ledipasvir/sofosbuvir (90mg/400mg): 12 weeks without ribavirin for treatment-naïve and treatment-experienced patients with or without compensated cirrhosis 5
• Ombitasvir/paritaprevir/ritonavir plus dasabuvir:
  • Genotype 1b without cirrhosis: 12 weeks without ribavirin 5
  • Genotype 1b with cirrhosis: 12 weeks with ribavirin 5
  • Genotype 1a without cirrhosis: 12 weeks with ribavirin 5
  • Genotype 1a with cirrhosis: 24 weeks with ribavirin 5

Genotype 2

• Sofosbuvir/velpatasvir: 12 weeks without ribavirin for all patients (treatment-naïve and experienced, with or without cirrhosis) 5, 1
• Sofosbuvir/daclatasvir (400mg/60mg): 12 weeks without ribavirin as alternative 5

Genotype 3 (Requires Special Attention)

• Treatment-naïve without cirrhosis: Sofosbuvir/velpatasvir 12 weeks without ribavirin 5, 1
• Treatment-experienced without cirrhosis OR any patient with compensated cirrhosis:
  • If NS5A resistance testing unavailable: Sofosbuvir/velpatasvir 12 weeks WITH ribavirin 5, 1
  • If NS5A Y93H mutation detected: Sofosbuvir/velpatasvir 12 weeks WITH ribavirin 5
  • If NS5A Y93H mutation absent: Sofosbuvir/velpatasvir 12 weeks WITHOUT ribavirin 5
• Alternative: Sofosbuvir/daclatasvir with similar duration and ribavirin considerations 5
• Ribavirin contraindication or intolerance: Extend sofosbuvir/velpatasvir to 24 weeks without ribavirin 5

Genotypes 4,5, and 6

• Sofosbuvir/velpatasvir: 12 weeks without ribavirin for treatment-naïve and treatment-experienced patients with or without compensated cirrhosis 5, 1

Critical Testing and Monitoring

Pre-Treatment Testing

• Test ALL patients for hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) before initiating HCV treatment 2, 3
• HBV reactivation has caused fulminant hepatitis, hepatic failure, and death in HCV/HBV coinfected patients receiving DAAs 2
• Genotype testing to guide regimen selection (though pangenotypic regimens eliminate this need) 1
• Assess cirrhosis status (imaging, FibroScan, or biopsy) as this affects treatment duration 1, 3

Post-Treatment Monitoring

• Monitor HCV RNA at baseline, during treatment, end of treatment, and 12 weeks post-treatment to assess SVR 1
• Patients with cirrhosis require continued hepatocellular carcinoma surveillance with ultrasound every 6 months even after achieving SVR 1

Special Populations

HIV Coinfection

• Use same HCV treatment regimens as HIV-negative patients 1, 2
• Carefully evaluate drug-drug interactions with antiretroviral therapy before initiating DAAs 1, 3
• Sofosbuvir/velpatasvir achieved 92-100% SVR rates in HIV-coinfected patients 6

Renal Impairment

• Glecaprevir/pibrentasvir can be used in patients with any degree of renal impairment including those on dialysis 3
• Sofosbuvir-containing regimens require dose adjustment considerations in severe renal impairment 2

Common Pitfalls and Caveats

Resistance Testing Challenges

• NS5A resistance testing for genotype 3 is technically challenging and reliable results are not guaranteed in all cases 5
• When resistance testing is unavailable for genotype 3 patients with cirrhosis or treatment experience, default to adding ribavirin 5

Drug-Drug Interactions

• Proton pump inhibitors, H2-receptor antagonists, and antacids can significantly reduce DAA absorption 1
• Antiretroviral drugs, particularly protease inhibitors and certain integrase inhibitors, require careful interaction review 1, 3
• Always check for interactions before prescribing, particularly in patients on multiple medications 1

Treatment Failure Considerations

• Patients previously treated with NS5A inhibitors require 16 weeks of glecaprevir/pibrentasvir (genotype 1) 3
• Patients previously treated with NS3/4A protease inhibitors require 12 weeks of glecaprevir/pibrentasvir (genotype 1) 3
• Baseline resistance-associated substitutions do not appear to significantly impair SVR with sofosbuvir/velpatasvir in treatment-naïve patients 7, 8

Adverse Effects

• Most common adverse effects with sofosbuvir/velpatasvir: fatigue, headache, nausea, nasopharyngitis (≥10% incidence) 6
• Ribavirin-containing regimens: monitor hemoglobin and adjust ribavirin dose based on hemoglobin levels and creatinine clearance 2
• Serious adverse events are rare (2% with sofosbuvir/velpatasvir) 8