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

Treatment of Chronic Hepatitis C Virus (HCV) Infection

Recommended First-Line Treatment Regimens

For chronic HCV infection, prescribe either sofosbuvir/velpatasvir 400mg/100mg once daily for 12 weeks OR glecaprevir/pibrentasvir for 8-12 weeks (depending on cirrhosis status), as these pangenotypic regimens achieve SVR rates of 98% across all genotypes. 1, 2, 3

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IPD (Inpatient) and OPD (Outpatient) Prescription Format

Pre-Treatment Assessment Required:

• Test for HBV coinfection (HBsAg and anti-HBc) before initiating any DAA therapy, as HBV reactivation can cause fulminant hepatitis and death 4
• Determine HCV genotype if available and affordable to optimize treatment selection 2
• Assess fibrosis stage using noninvasive methods or biopsy to determine treatment duration 3
• Screen for drug-drug interactions, particularly with antiretrovirals, cardiac medications, and acid-suppressing agents 3

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Treatment Regimens by Genotype and Clinical Status

Genotype 1a (Treatment-Naïve, No Cirrhosis):

Option 1 (Preferred):

• Sofosbuvir/Velpatasvir 400mg/100mg PO once daily × 12 weeks 1, 3

Option 2:

• Ledipasvir/Sofosbuvir 90mg/400mg PO once daily × 12 weeks 5, 4
• Note: Can consider 8 weeks if HCV RNA <6 million IU/mL 4

Option 3:

• Sofosbuvir 400mg + Simeprevir 150mg PO once daily × 12 weeks 5
• Critical caveat: Only use if NS3 Q80K variant is NEGATIVE on resistance testing 5, 1

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Genotype 1a (Treatment-Naïve, With Compensated Cirrhosis):

Option 1:

• Sofosbuvir/Velpatasvir 400mg/100mg PO once daily × 12 weeks 1, 3

Option 2:

• Ledipasvir/Sofosbuvir 90mg/400mg PO once daily × 12 weeks 4

Option 3:

• Glecaprevir/Pibrentasvir PO once daily × 12 weeks (extended from 8 weeks due to cirrhosis) 1, 3

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Genotype 1a (Treatment-Experienced, With Compensated Cirrhosis):

Preferred:

• Ledipasvir/Sofosbuvir 90mg/400mg PO once daily × 24 weeks 4

Alternative:

• Ledipasvir/Sofosbuvir 90mg/400mg + weight-based ribavirin (1000mg if <75kg, 1200mg if ≥75kg) PO divided BID × 12 weeks 4

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Genotype 1b (Treatment-Naïve or Experienced, No Cirrhosis):

Option 1:

• Ledipasvir/Sofosbuvir 90mg/400mg PO once daily × 12 weeks 5, 4

Option 2:

• Paritaprevir/Ritonavir/Ombitasvir + Dasabuvir (fixed-dose) PO once daily × 12 weeks 5

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Genotype 2 (All Patients):

Preferred:

• Sofosbuvir/Velpatasvir 400mg/100mg PO once daily × 12 weeks (no ribavirin needed) 5, 1

Alternative (if above unavailable):

• Sofosbuvir 400mg + weight-based ribavirin (1000mg if <75kg, 1200mg if ≥75kg) PO divided BID × 12 weeks 5
• Extend to 16-20 weeks if cirrhotic and treatment-experienced 5

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Genotype 3 (Treatment-Naïve, No Cirrhosis):

Preferred:

• Sofosbuvir/Velpatasvir 400mg/100mg PO once daily × 12 weeks (no ribavirin) 5, 1

Alternative:

• Daclatasvir 60mg + Sofosbuvir 400mg PO once daily × 12 weeks 5

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Genotype 3 (Treatment-Experienced or With Cirrhosis):

Preferred:

• Sofosbuvir/Velpatasvir 400mg/100mg + weight-based ribavirin (1000mg if <75kg, 1200mg if ≥75kg) PO divided BID × 12 weeks 5, 1

Alternative (if NS5A RAS Y93H absent):

• Sofosbuvir/Velpatasvir 400mg/100mg PO once daily × 12 weeks (no ribavirin) 5

Alternative (if NS5A RAS Y93H present OR ribavirin contraindicated):

• Sofosbuvir/Velpatasvir 400mg/100mg PO once daily × 24 weeks (no ribavirin) 5

Alternative (Treatment-Experienced with Cirrhosis):

• Daclatasvir 60mg + Sofosbuvir 400mg PO once daily × 24 weeks ± ribavirin 5

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Genotype 4,5, or 6 (All Patients):

Preferred:

• Sofosbuvir/Velpatasvir 400mg/100mg PO once daily × 12 weeks 1, 2

Alternative (Genotype 4):

• Ledipasvir/Sofosbuvir 90mg/400mg PO once daily × 12 weeks 5
• Add ribavirin if cirrhotic 5

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Special Populations

Decompensated Cirrhosis (Child-Pugh B or C):

• Ledipasvir/Sofosbuvir 90mg/400mg + ribavirin (start 600mg, titrate to weight-based dosing) PO divided BID × 12 weeks 4
• Sofosbuvir/Velpatasvir + ribavirin × 12 weeks 1

Liver Transplant Recipients (Genotype 1 or 4):

• Ledipasvir/Sofosbuvir 90mg/400mg + weight-based ribavirin PO divided BID × 12 weeks 4

HIV Coinfection:

• Use same HCV regimens as HIV-negative patients 1, 2
• Critical: Check for drug-drug interactions with antiretrovirals and adjust doses accordingly 3

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Monitoring Protocol

During Treatment:

• HCV RNA at baseline, weeks 4 and 12, end of treatment 3
• Monitor for HBV reactivation in coinfected patients (ALT, HBV DNA) 4

Post-Treatment:

• HCV RNA at 12 weeks post-treatment (SVR12 = cure) 3
• For cirrhotic patients: Continue HCC surveillance with ultrasound every 6 months indefinitely, even after SVR 1, 3

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Critical Drug Interactions and Contraindications

Absolute Contraindications:

• Do NOT use DAAs with strong CYP3A4 inducers (carbamazepine, phenytoin, phenobarbital, rifampin) as they decrease DAA levels and cause treatment failure 3
• However, real-world data shows some patients achieved SVR despite this interaction when alternatives were unavailable 6

Ledipasvir/Sofosbuvir Specific:

• Proton pump inhibitors: Limit to omeprazole 20mg equivalent, take 4 hours before ledipasvir/sofosbuvir 4
• H2 antagonists: Take simultaneously or 12 hours apart 4

Paritaprevir/Ritonavir/Ombitasvir:

• Avoid salmeterol and other CYP3A4 substrates 5

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Common Pitfalls to Avoid

• Do NOT defer treatment in F3-F4 fibrosis patients—they have the most urgent need for viral eradication 3
• Do NOT use sofosbuvir + simeprevir in genotype 1a cirrhotic patients with Q80K polymorphism—SVR rates drop significantly 5, 1
• Do NOT use ledipasvir/sofosbuvir for genotype 3—ledipasvir has poor activity against this genotype 5
• Do NOT stop HCC surveillance after SVR in cirrhotic patients—cancer risk persists 1, 3
• Do NOT use sofosbuvir + ribavirin alone for genotype 3—it is suboptimal with high relapse rates 5

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Treatment Failure Management

If Failed NS5A Inhibitor (ledipasvir, daclatasvir, velpatasvir):

• Sofosbuvir + Simeprevir + Daclatasvir + ribavirin × 24 weeks 5
• OR Sofosbuvir + Paritaprevir/Ritonavir/Ombitasvir ± Dasabuvir + ribavirin × 12-24 weeks (depending on genotype and fibrosis) 5

If Failed Sofosbuvir Alone:

• Retreat with any NS5A-containing regimen (ledipasvir/sofosbuvir, sofosbuvir/velpatasvir, daclatasvir/sofosbuvir) + ribavirin × 12-24 weeks 5

General Retreatment Principles:

• Use 12 weeks + ribavirin for F0-F2 fibrosis 5
• Use 24 weeks + ribavirin for F3-F4 fibrosis 5
• Consider resistance testing if available, though optimal algorithms remain undefined 5, 7