What is the recommended treatment for a patient with genotype 1a hepatitis C (HCV)?

Treatment of Hepatitis C Genotype 1a

For treatment-naïve patients with HCV genotype 1a, the preferred first-line regimen is sofosbuvir/velpatasvir 400mg/100mg once daily for 12 weeks, achieving 98% sustained virologic response (SVR) rates regardless of cirrhosis status. 1, 2

First-Line Treatment Options

The most current guidelines prioritize pangenotypic direct-acting antiviral (DAA) regimens that work across all HCV genotypes:

Preferred Regimen

• Sofosbuvir/velpatasvir 400mg/100mg once daily for 12 weeks is the top choice for all patients with genotype 1a, with or without compensated cirrhosis 1, 2, 3
• This single-tablet regimen is taken with or without food and achieves SVR rates of 98% 1, 2

Alternative First-Line Option

• Glecaprevir/pibrentasvir offers comparable efficacy with treatment duration based on cirrhosis status: 1, 4, 5
  • 8 weeks for patients without cirrhosis 1, 4, 5
  • 12 weeks for patients with compensated cirrhosis (Child-Pugh A) 1, 4, 5

Older Genotype-Specific Regimens (Still Effective but Less Preferred)

While pangenotypic regimens are now standard, earlier genotype 1a-specific options remain effective:

• Ledipasvir 90mg/sofosbuvir 400mg once daily: 6, 4

  • 12 weeks for patients without cirrhosis 6, 4
  • 24 weeks for patients with compensated cirrhosis 6, 4
  • Can add weight-based ribavirin (1000mg if <75kg, 1200mg if ≥75kg) for treatment-experienced patients 6, 4

• Paritaprevir/ritonavir/ombitasvir plus dasabuvir with ribavirin: 6

  • 12 weeks with weight-based ribavirin for patients without cirrhosis 6
  • 24 weeks with weight-based ribavirin for patients with compensated cirrhosis 6

• Sofosbuvir 400mg plus simeprevir 150mg: 6

  • Only use if Q80K polymorphism testing is negative 6
  • 12 weeks for non-cirrhotic patients, 24 weeks for cirrhotic patients 6
  • Critical caveat: Patients with cirrhosis and the Q80K variant have significantly lower SVR rates (avoid this regimen in Q80K-positive cirrhotic patients) 6

Pre-Treatment Requirements

Before initiating DAA therapy, complete the following assessments:

• HBV screening: Measure hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) to identify HBV coinfection risk 5, 3
• HCV RNA quantitative testing to confirm active viremia 1, 2
• Genotype and subtype determination (distinguishing 1a from 1b is essential as treatment differs) 6, 1, 4
• Fibrosis staging using non-invasive methods (FibroScan, APRI, FIB-4) or liver biopsy if uncertainty exists 6, 1
• Comprehensive drug-drug interaction screening before prescribing any DAA regimen 6, 1, 4

Treatment Modifications by Clinical Scenario

Compensated Cirrhosis (Child-Pugh A)

• Use the same pangenotypic regimens as non-cirrhotic patients 1, 2
• Extend glecaprevir/pibrentasvir to 12 weeks (from 8 weeks) 1, 4, 5
• Extend older genotype-specific regimens (ledipasvir/sofosbuvir to 24 weeks, paritaprevir/ritonavir/ombitasvir/dasabuvir to 24 weeks with ribavirin) 6, 4

Decompensated Cirrhosis (Child-Pugh B or C)

• Sofosbuvir/velpatasvir plus weight-based ribavirin for 12 weeks 2, 3
• Ribavirin dosing: 1000mg daily if <75kg, 1200mg daily if ≥75kg, divided twice daily with food 3

Treatment-Experienced Patients

• For prior NS5A inhibitor failure: Extend treatment to 16 weeks with glecaprevir/pibrentasvir 5
• For prior NS3/4A protease inhibitor failure: 12 weeks with glecaprevir/pibrentasvir 5
• Consider adding ribavirin to sofosbuvir/daclatasvir for 12 weeks if NS5A resistance-associated substitutions (RAS) are present 6, 4

Critical Drug-Drug Interactions

Absolute contraindications that significantly reduce DAA efficacy include: 1, 4

• P-glycoprotein (P-gp) inducers (rifampin, St. John's wort) 1, 4
• Moderate-to-strong CYP3A4 inducers (carbamazepine, phenytoin, phenobarbital) 1, 4
• Efavirenz-containing antiretroviral regimens 1

Important interactions requiring dose adjustments or monitoring: 6, 4

• Ledipasvir/sofosbuvir with proton pump inhibitors (may reduce absorption) 6
• Paritaprevir/ritonavir/ombitasvir/dasabuvir with salmeterol and other CYP3A4 substrates 6
• Daclatasvir requires dose adjustment with certain HIV medications (30mg with atazanavir/ritonavir, 90mg with efavirenz) 6

Real-world evidence caveat: One small case series showed that all 5 patients achieved SVR despite concomitant use of first-generation anticonvulsants with DAAs, though this contradicts guideline recommendations and should not be routinely attempted 7

Monitoring Protocol

During Treatment

• Measure HCV RNA at baseline, weeks 4 and 12, and end of treatment 1, 2
• Monitor for adverse events (generally mild with DAA-only regimens; more common with ribavirin-containing regimens) 6, 8

Post-Treatment

• SVR12 (undetectable HCV RNA 12 weeks after treatment completion) is the primary measure of cure 1, 2
• Achieved in >99% of patients who reach this endpoint 2

Long-Term Surveillance

• For patients with cirrhosis: Continue hepatocellular carcinoma (HCC) surveillance with ultrasound every 6 months indefinitely, even after achieving SVR 1, 4, 2
• This is critical as cirrhotic patients remain at elevated HCC risk despite viral eradication 1

Common Pitfalls to Avoid

• Do not defer treatment in patients with advanced fibrosis (F3-F4), as these patients have the most urgent need and greatest short-term benefit from viral eradication 1
• Always test for Q80K polymorphism before using sofosbuvir/simeprevir in cirrhotic genotype 1a patients, as Q80K-positive patients have significantly lower SVR rates with this regimen 6, 4
• Do not treat genotype 1 that cannot be subtyped as genotype 1b—always treat as genotype 1a to ensure adequate treatment intensity 6
• Verify all drug-drug interactions before prescribing, particularly with antiretrovirals, cardiac medications, anticonvulsants, and acid-suppressing agents 6, 1, 4
• Resistance testing for NS5A RAS is optional but helpful in treatment-experienced patients to guide ribavirin addition and treatment duration 6, 4

Expected Outcomes

With modern pangenotypic DAA regimens, expected outcomes include: 2

• SVR rates exceeding 95-98% in most patient populations 1, 2, 8
• Improvement in liver histology and decreased risk of cirrhotic complications 2
• Reduced occurrence of hepatocellular carcinoma 2
• Improved survival rates and resolution of extrahepatic manifestations 2
• Low rates of serious adverse events (<10%) and treatment discontinuation 8